Comparison of the effects of amlodipine and losartan on 24-hour ambulatory blood pressure in hypertensive patients

Effects of amlodipine (AML), a long-acting calcium antagonist, and losartan (LOS), an angiotensin II receptor antagonist, on 24-hr blood pressure profile were compared in 15 patients with essential hypertension. After 4 weeks of placebo period, the patients were treated with AML or LOS in a random crossover design for 12-16 weeks each. Either drug was given once daily at 0800 and the doses were titrated so that the office blood pressure was reduced lower than 140/90mmHg. At the end of each period, 24-hr blood pressure was monitored. Average office blood pressure was lowered from 158 +/- 2/ 98 +/- 2 mmHg to 134 +/- 1/87 +/- 1 mmHg by AML and 134 +/- 2/88 +/- 1 mmHg by LOS. Average 24-hr blood pressure was also reduced from 144 +/- 3/ 92 +/- 2 mmHg to 131 +/- 2/84 +/- 2 mmHg by AML and 135 +/- 3/85 +/- 2 mmHg by LOS. The averaged 24-hr systolic blood pressure was significantly lower in AML than in LOS (p < 0.05). Then, the 24-hr blood pressure was analyzed for four segments; morning (0530-0900 h), daytime (0930-1800 h), evening (1830-2300 h) and night (2330-0500 h). Although the daytime blood pressure was comparable between AML and LOS, systolic blood pressure in the evening and morning hours were lower in AML than in LOS (133 +/- 2 vs. 138 +/- 3mmHg,p<0.01; 129 +/- 3 vs. 134 +/- 4,p<0.05). Troughtopeakratio of antihypertensive effect on systolic blood pressure was significantly greater in AML than in LOS (62 +/- 5% vs. 55 +/- 4%, p < 0.05). Either drug did not cause reflective increase in pulse rate over 24 hours. These results suggest that both AML and LOS are equally effective in lowering daytime blood pressure without eliciting reflex tachycardia, however, the antihypertensive effect of AML lasts longer than that of LOS. Such information seems important to achieve 24-hr blood pressure control using these drugs.     

Decline of Renal Function Is Associated with Proteinuria and Systolic Blood Pressure in the Morning in Diabetic Nephropathy

The aim of this study was to investigate a significance of increased proteinuria in the morning and the effects of antihypertensive treatment on proteinuria and arterial blood pressure in the progression of chronic renal insufficiency in type 2 diabetic patients with hypertension and nephropathy. In three 24-hr urine samples and blood pressure monitoring, separated into a night-and daytime and spot urine in the morning, variation in protein-creatinine ratio (g/g) and blood pressure were assessed in 24 (58 ± 3 years old; M/F: 17/7) diabetic patients with hypertension and nephropathy. Furthermore, the effects of antihypertensive therapy of combinations of angiotensin converting enzyme (ACE) inhibitor, calcium antagonists, diuretics, and α1 blocker were evaluated in 3 years. Home blood pressure measurement was carried out every month and 24-hr urine was collected every 2 months. The baseline urine excretion of protein-creatinine ratio and blood pressure were (1.22 ± 0.13 g/g creatinine: 154/96 ± 6/5 mmHg) in daytime and (1.39 ± 0.13: 168/88 ± 15/7) in the morning. At the end of the study, significant associations among a decline of 24-hr creatinine clearance and both of the urine excretion of protein-creatinine ratio (r = 0.47, p < .01) and the levels of systolic blood pressure (r = 0.46, p < .01) and between the levels of systolic blood pressure and the urine excretion of protein-creatinine ratio in the morning (r = 0.57, p < .001) were demonstrated. However, there were no significant associations among other variables. Analysis of patients who had systolic blood pressure in the morning less than 140 mmHg revealed that 65% of these patients received doxazosin-averaged doses of 4.8 ± 1.5 mg daily. The levels of both blood pressure and proteinuria-creatinine ratio in the morning mainly associate with progression of renal function in diabetic patients with hypertension and nephropathy.     

Ambulatory Blood Pressure Variability Is Increased in Diabetic Hypertensives

The purpose of this study was to examine the possible difference in the 24-hr BP profile—including short-term BP variability, assessed as the standard deviation—between diabetic and non-diabetic hypertensives. We measured 24-hr ambulatory BP in 11 diabetic hypertensives (diabetic HT) and 10 non-diabetic hypertensives (non-diabetic HT) who were hospitalized for the educational program in our hospital and were under stable salt intake. Renal function and sleep apnea were also estimated. There were no significant differences in 24-hr systolic BP (141 mmHg vs. 135 mmHg, ns), daytime systolic BP (143 mmHg vs. 138 mmHg, ns), and nighttime systolic BP (135 mmHg vs. 130 mmHg, ns) between diabetic HT and non-diabetic HT. The values of 24‐hr HR (69.7 beats/min vs. 65.2 beats/min, ns) and 24-hr HR variability (9.9 beats/min vs. 10.1 beats/min, ns) were also similar between the groups. Interestingly, diabetic HT had a significantly greater 24-hr systolic and diastolic BP variability than non-diabetic HT (18.2 mmHg vs. 14.5 mmHg, p < 0.05; 11.5 mmHg vs. 9.6 mmHg, p < 0.05, respectively). The values for creatinine clearance, urinary protein excretion, and apnea-hypopnea index were similar between the groups. Bivariate linear regression analysis demonstrated that fasting blood glucose was the primary determinant of 24-hr diastolic BP variability (r = 0.661, p < 0.01). Multiple stepwise regression analysis revealed that fasting blood glucose was a significant and independent contributor to 24-hr systolic BP variability (r = 0.501, p < 0.05). Taken together, these results demonstrate that BP variability is increased in diabetic hypertensives. Furthermore, it is possible that an elevation of fasting blood glucose may contribute to the enhanced BP variability in hypertensives.     

Oxidative Stress in the Dahl Salt-Sensitive Hypertensive Rat

Oxidative stress has been proposed as important in the pathogenesis of hypertension. Measurement of 8-iso prostaglandin F_2α(8-ISO) is introduced for evaluating oxidative stress in vivo. 8-ISO is the major urinary metabolite of F₂-isoprostanes and is formed nonenzymatically from the attack of superoxide radicals on arachidonic acid. We examined the oxidative stress level in the Dahl salt-sensitive (Dahl-S) rats and the Dahl salt-resistant (Dahl-R) rats. Dahl-S and Dahl-R rats were fed either a high salt diet (8% NaCl; HS) or low salt diet (0.3% NaCl; LS) for 3 weeks, and systolic blood pressure (SBP) and 24-hr urinary excretion of 8-ISO (U-8-ISO) were measured. In Dahl-S rats, the high salt diet induced hypertension (139 ± 3 mmHg in LS versus 186 ± 2 mmHg in HS, p < .05) and significantly increased the U-8-ISO (24.9 ± 3.6 ng/24 hr in LS versus 63.2 ± 14.6 ng/24 hr in HS, p < .05). No significant difference in blood pressure or U-8-ISO was observed between high-salt and low-salt treated Dahl-R rats. U-8-ISO concentration was correlated with SBP in all four experimental groups (r = 0.866). Moreover, urinary 8-hydroxy-2′-deoxyguanosine (U-8-OHdG), which is one of the most commonly used markers for evaluation of oxidative stress, was higher in Dahl-S-8% rats than in Dahl-S-0.3% rats (136.1 ± 48.4 ng/24 hr in LS versus 322.8 ± 46.7 ng/24 hr in HS, p < .05), and U-8-OHdG was correlated with SBP (r = 0.681) in Dahl-S rats. These results suggest oxygen radicals are involved in the pathogenesis of hypertension.     

The effect of Mid-Day Sleep on blood pressure levels in patients with arterial hypertension

Study objectivesLifestyle changes decrease blood pressure (BP) levels by 3-5 mmHg in hypertensive patients. We assessed the effect of mid-day sleep on BP levels in hypertensive patients.MethodsWe prospectively studied two hundred and twelve hypertensive patients. Mid-day sleep duration, lifestyle habits, anthropometric characteristics, office BP, ambulatory BP monitoring, pulse wave velocity (PWV), augmentation index (AI) were recorded. A standard echocardiographic evaluation was performed.Results53.8% were females, mean age was 62.5±11.0 years and mean body mass index was 28.9±5.4kg/m². Mean average 24h systolic and diastolic BP (SBP & DBP) was 129.9±13.2/76.7±7.9 mmHg respectively. The majority was non-smokers (70.3%) and did not have diabetes (74.7%). The mean midday sleep duration was 48.7±54.3 min. Average 24h SBP (127.6±12.9 mmHg vs 132.9±13.1 mmHg), average daytime SBP & DBP were lower in patients who sleep at midday, compared to those who do not (128.7±13/76.2±11.5 vs 134.5±13.4/79.5±10.4 mmHg) (p<0.005). The effect was not correlated to the dipping status. Midday sleep duration was negatively correlated with average 24h SBP & daytime SBP. In a linear regression model, for every 60 min of midday sleep, 24h average SBP decreases by 3 mmHg (p<0.001). There were no differences in the number of antihypertensive medications, PWV, AI or echocardiographic indices between study groups.ConclusionsMid-day sleep significantly decreases average 24h and daytime SBP/DBP in hypertensives. Its effect seems to be as potent as other well-established lifestyle changes and is independent of dipping status.     

Kidney resistive index relates to variations of home blood pressure in chronic kidney diseases

Background: Kidney resistive index (RI) correlates with tubulointerstitial changes and predicts renal prognosis. Most patients with chronic kidney diseases (CKDs) manifest high blood pressure and atherosclerotic cardiovascular diseases. In addition, various atherosclerotic indexes relate to variations in blood pressure.Methods: Subjects were 70 CKD patients, who visited our office and agreed to measure home blood pressure and receive renal ultrasonography. Cross-sectional analyses were performed.Results: Patient age was averaged 61 ± 15 (SD) y/o and 60% were male. Mean serum creatinine and proteinuria were 1.2 ± 0.5 mg/dl and 0.2 ± 0.5 g/gCr, respectively. Office blood pressure and kidney RI were 128 ± 17/75 ± 11 mmHg and 0.66 ± 0.08, respectively. Multivariate regression analysis revealed that age and office blood pressure independently correlated to kidney RI (p < 0.05 for each). Home blood pressure was averaged 122 ± 7/70 ± 6 mmHg. Both standard deviation and the maximal–minimal difference in home systolic blood pressure related to kidney RI (p < 0.05).Conclusions: The present results indicate that office blood pressure correlates to kidney RI, which predicts renal prognosis. In addition, our data implicate that kidney RI relates to variations in home systolic blood pressure, and suggest that kidney RI may be a good index for atherosclerosis in CKD patients.     

Efficacy of once-daily lisinopril monotherapy in systemic hypertension

Lisinopril is a new, long-acting angiotensin-converting enzyme inhibitor formulated for once-daily treatment of hypertension. This study assessed the 24-h efficacy and tolerability of lisinopril in Chinese patients with mild to moderate hypertension of World Health Organization Stages I to II. A total of 30 patients aged 30 to 60 years (mean 47 ± 9) entered a 2-week washout period. All patients had ambulatory diastolic blood pressure (BP) > 90 mmHg and were given active treatment with lisinopril for 4 to 7 weeks. The dose of lisinopril was titrated from 10 to 40 mg daily (at 8-9 A. M.). In each patient, 24-h ambulatory blood pressure (BP) monitoring (SpaceLabs 90202) was performed twice, once before and once following treatment. Mean 24-hour systolic/diastolic BPs after lisinopril were significantly decreased compared with baseline values (132 ± 12/86 ± 7 vs. 150 ± 11/98 ± 7 mmHg; p < 0.0005/ 0.0005). The average dose of lisinopril was 14.5 ± 5 mg daily after a titration period of 5 weeks of treatment. Mean daytime (6 A. M. to 6 P. M.) BP decreased from 152 ± 11/100 ± 8 to 134 ± 12/87 ± 8 mmHg (p < 0.0005/0.0005) and nighttime (6 P.M. to 6 A. M.) BP from 147 ± 14/95 ± 9 to 128 ± 14/83 ± 8 mmHg ( p < 0.0005/0.0005). BP reduction was more pronounced during the night. Before treatment, the circadian variation showed a peak BP at 11 A. M. and nadir at 3 P. M. After treatment, significant BP reduction (p < 0.0005/0.0005) was seen throughout the 24-h period. The circadian rhythm of BP was preserved as indicated by similar BP standard deviations (14 ± 3/11 ± 2 vs. 13 ± 3/10 ± 2 mmHg). Mean heart rate increased from 76 to 80 beats/min (p < 0.05). Four patients reported having a nonproductive cough. Thus, lisinopril administered as once-daily monotherapy provided effective BP control over a 24-h period with preserved circadian rhythm.     

Diurnal Variation in Blood Pressure in Insulin-dependent Diabetic Smokers and Non-smokers with and without Microalbuminuria

In subjects with essential hypertension, loss of the normal nocturnal dip in blood pressure is associated with a greater risk of developing end-organ complications. In subjects with diabetes, smoking carries a similar association. To assess whether these factors may have an aetiological and synergistic role in the vascular complications of diabetes, 24-hour blood pressure monitoring was performed in insulin-dependent diabetic (IDDM) patients with normal albumin excretion (n = 19) and microalbuminuria (n = 21) of comparable age and duration of diabetes, and with no evidence of autonomic neuropathy or hypertension. The potential influence of smoking was examined by subdividing the groups, depending on smoking status. Ten of the microalbuminuric group and 9 of the normoalbuminuric group were current smokers, the remaining patients never having smoked. There was a significant difference between mean (±SD) daytime vs nocturnal blood pressure in patients with normal albumin excretion (114 ± 3/70 ± 4 vs 102 ± 3/62 ± 3 mmHg; p < 0.001) and microalbuminuria (109 ± 5/75 ± 5 vs 101 ± 3/65 ± 4 mmHg; p < 0.001) but mean blood pressure values did not differ significantly between the groups. A similar fall in nocturnal blood pressure was found in smokers and non-smokers with and without microalbuminuria (p < 0.001), but there was no difference between the mean blood pressure values in the different subgroups. In conclusion, normotensive IDDM patients, who do not have autonomic neuropathy, retain a significant diurnal variation in blood pressure, irrespective of smoking habit or presence of microalbuminuria. © 1997 by John Wiley & Sons, Ltd.     

Negative association between plasma aldosterone concentration/plasma renin activity and morning blood pressure surge in never-treated hypertensive patients

Morning blood pressure (BP) surge (MS) has been known to be a predictor of cardiovascular events. Currently, few studies have evaluated the underlying mechanism underlying MS, which may include neurohormonal factors and the renin–angiotensin–aldosterone system (RAAS). This study aimed to examine plasma aldosterone concentration (PAC) and plasma renin activity (PRA) and BP parameters with or without MS in never-treated subjects with essential hypertension. This cross-sectional study included a total of 261 patients (mean age: 48.8 years; 60.5% male) with never-treated essential hypertension who were registered in a working group at The Catholic University of Korea. The patients were divided into the MS group, which was defined as having the highest quartile of morning BP increase from sleep (>31?mmHg; n?=?66) and the non-MS group (≤31?mmHg; n?=?195). We collected 24-h ambulatory BP, pulse wave velocity, ankle brachial index, PAC and PRA from all patients. The measured PAC and PRA were lower in the MS group than in the non-MS group (PAC: 9.0?±?5.4?ng/dl versus 12.2?±?8.7?ng/dl, p?p?=?0.002). The MS group had greater variations in daytime, nighttime and 24-h systolic blood pressure (SBPs) than the non-MS group (24-h SBP: 15.6?±?4.4?mm Hg for the non-MS group and 18.9?±?4.9?mmHg for the MS group; p?相似文献   

Assessment of baroreceptor-cardiac reflex sensitivity using time domain analysis in patients with IDDM and the relation to left ventricular mass index

Summary Autonomic dysfunction in insulin-dependent diabetic (IDDM) patients has been associated with abnormalities of left ventricular function and an increased risk of sudden death. A group of 30 patients with IDDM and 30 age, sex and blood pressure matched control subjects underwent traditional tests of autonomic function. In addition, baroreceptor-cardiac reflex sensitivity (BRS) was assessed using time domain (sequence) analysis of systolic blood pressure and pulse interval data recorded non-invasively using the Finapres beat-to-beat blood pressure recording system. ’Up BRS' sequences–increases in systolic blood pressure associated with lengthening of R-R interval, and ’down BRS' sequences–decreases in systolic blood pressure associated with shortening of R-R interval were identified and BRS calculated from the regression of systolic blood pressure on R-R interval for all sequences. We also assessed heart rate variability using power spectral analysis and, after expressing components of the spectrum in normalised units, assessed sympathovagal balance from the ratio of low to high frequency powers. IDDM subjects underwent 2-D echocardiography to assess left ventricular mass index. Standard tests of autonomic function revealed no differences between IDDM patients and control subjects, but dramatic reductions in baroreceptor-cardiac reflex sensitivity were detected in IDDM patients. ’Up BRS' when supine was 11.2 ± 1.5 ms/mmHg (mean ± SEM) compared with 20.4 ± 1.95 in control subjects (p < 0.003) and when standing was 4.1 ± 1.9 vs 7.6 ± 2.7 ms/mmHg (p < 0.001). Down BRS when supine was 11.5 ± 1.2 vs 22 ± 2.6 (p < 0.001) and standing was 4.4 ± 1.9 vs 7.3 ± 2.5 ms/mmHg (p < 0.003). There were significant relations between impairment of the baroreflex and duration of diabetes (p < 0.001) and poor glycaemic control (p < 0.001). From a fast Fourier transformation of supine heart rate data and using a band width of 0.05–0.15 Hz as low-frequency and 0.2–0.35 Hz as high frequency total spectral power of R-R interval variability was significantly reduced in the IDDM group for both low-frequency (473 ± 62.8 vs 746.6 ± 77.6 ms² p = 0.002) and high frequency bands 125.2 ± 12.9 vs 459.3 ± 89.8 ms² p < 0.0001. When the absolute powers were expressed in normalised units the ratio of low frequency to high frequency power (a measure of sympathovagal balance) was significantly increased in the IDDM group (2.9 ± 0.53 vs 4.6 ± 0.55, p < 0.002 supine: 3.8 ± 0.49 vs 6.6 ± 0.55, p < 0.001 standing). Thus, time domain analysis of baroreceptor-cardiac reflex sensitivity detects autonomic dysfunction more frequently in IDDM patients than conventional tests. Impaired BRS is associated with an increased left ventricular mass index and this abnormality may have a role in the increased incidence of sudden death seen in young IDDM patients. [Diabetologia (1996) 39: 1385–1391] Received: 9 April 1996 and in revised form: 19 July 1996     

Effect of weight loss on sympatho-vagal balance in subjects with grade-3 obesity: restrictive surgery versus hypocaloric diet

Few and mostly uncontrolled studies indicate that weight loss improves heart rate variability (HRV) in grade-3 obesity. The aim of this study was to compare in grade-3 obesity surgery and hypocaloric diet on clinical and metabolic variables and on autonomic indices of HRV. Twenty-four subjects (body mass index, BMI 45.5 ± 9.13 kg/m²) underwent surgery (n = 12, gastric banding, LAGB) or received hypocaloric diet (n = 12, 1,000–1,200 kg/day). Clinical [BMI, systolic blood pressure (SBP) and diastolic blood pressure (DBP), heart rate] and metabolic variables [glucose, cholesterol, HDL- and LDL-cholesterol, triglycerides, AST and ALT transaminases] and 24-h Holter electrocardiographic-derived HRV parameters [R–R interval, standard deviation of R–R intervals (SDNN); low/high-frequency (LF/HF) ratio, and QT interval] were measured at baseline and after 6 months. The two groups were identical at baseline. BMI (?7.5 ± 3.57 kg/m², mean ± SD), glucose (?24.1 ± 26.77 mg/dL), SBP (?16.7 ± 22.19 mmHg) and DBP (?6.2 ± 8.56 mmHg) decreased in LAGB subjects (p < 0.05) and remained unchanged in controls. At 6 months, SDNN increased in LAGB subjects (+25.0 ± 37.19 ms, p < 0.05) and LF/HF ratio diminished (2.9 ± 1.84 vs. 4.9 ± 2.78; p = 0.01), with no change in controls; LF (daytime) and HF (24 h and daytime) increased in LAGB subjects, with no change in controls. Decrease in BMI correlated with SBP and DBP decrease (p < 0.05), and DBP decrease correlated with HR decrease (p < 0.05) and QT shortening (p < 0.05). Weight loss is associated with improvement of glucose metabolism, of blood pressure, and with changes in time and frequency domain parameters of HRV; all these changes indicate recovery of a more physiological autonomic control, with increase in parasympathetic and reduction in sympathetic indices of HRV.     

Predictors of successful pulmonary balloon valvuloplasty: 10-year experience

At our institution, 55 infants and children (ages 0.3–21 yr, median 2.5 yr) underwent pulmonary balloon valvuloplasty between August 1983 and May 1993. Systolic pressure gradients fell acutely following balloon valvuloplasty from 63.5 ± 24.8 mmHg (mean ± standard deviation) to 26.7 ± 12.9 mmHg (P < 0.001) with a decrease in systolic pressure ratio from 0.81 ± 0.25 to 0.42 ± 0.12 (P < 0.0001). Fifty of the 55 patients had long-term echocardiographic evaluation performed >2 yr following balloon valvuloplasty. Thirty-four of the 50 patients (Group A; 68%) were classified as having successful (residual systolic gradients <25 mmHg, ventricular systolic pressure ratios <0.6) long-term outcomes. Their peak systolic gradients fell acutely from 58.8 ± 16.6 mmHg to 22.7 ± 11.2 mmHg (P < 0.001). At 4.6 ± 2.3 yr postvalvuloplasty, peak instantaneous pressure gradients were 17.8 ± 5.7 mmHg (P = ns vs. acute postvalvuloplasty). Fifteen of the 50 patients (Group B; 30%) had unsuccessful (residual systolic gradients ≥25 mmHg and/or ventricular systolic pressure ratios >0.6) long-term outcomes. Their peak instantaneous systolic gradients fell acutely from 76.5 ± 33.1 mmHg to 36.6 ± 11.4 mmHg (P < 0.05). At 3.8 ± 1.7 yr postvalvuloplasty, peak instantaneous pressure gradients were 35.1 ± 9.1 mmHg (P = ns vs. acute postvalvuloplasty). One 3-yr-old patient (Group C, 2%) required repeat balloon valvuloplasty on two separate occasions for recurrent stenosis. There was no significant prevalvuloplasty difference between Groups A and B with regard to age, weight, or Z scores of the pulmonary annull or balloon/annulus ratio; however, patients in Group A had significantly lower prevalvuloplasty gradients and lower systolic pressure ratios than patients in Group B. Total systolic gradient reduction between patients with successful and unsuccessful outcomes was not significantly different (Group A: 36.1 ± 16.6 mmHg; Group B: 41 ± 22.3 mmHg). At long-term follow-up, patients in Group A had fewer symptoms and a significantly lower rate of electrocardiographic right ventricular hypertrophy than Group B patients. Successful outcomes defined by our criteria following balloon valvuloplasty were achieved in 68% of patients with greatest long-term success in patients with prevalvuloplasty systolic gradients <60 mmHg and systolic pressure ratios <0.8. Intervention at lesser systolic gradients (40–60 mmHg) appears indicated to achieve lower long-term gradients and fewer symptoms as total systolic gradient reduction by this technique is limited. © 1996 Wiley-Liss, Inc.     

BLOOD PRESSURE REDUCTION IN THE MORNING YIELDS BENEFICIAL EFFECTS ON PROGRESSION OF CHRONIC RENAL INSUFFICIENCY WITH REGRESSION OF LEFT VENTRICULAR HYPERTROPHY

Self-monitoring values of blood pressure may better reflect the average long-term blood pressure value than sporadic measurements in the physician's office and be more useful for blood pressure control. In the present study, we compared the results of self-monitoring of blood pressure values, especially in the morning, with office blood pressure, and related these to progression of chronic renal insufficiency and left ventricular hypertrophy (LVH). Thirty-four patients were selected from 316 subjects with chronic renal insufficiency (average serum creatinine 1.72 ± 0.15 mg/dl, mean age 52.6 ± 3.5 yrs) in accordance with the following criteria office blood pressure was less than 140/90 mmHg, blood pressure was controlled with amlodipine (5–20 mg/day) combined with benazepril (2.5 mg/day), morning blood pressure was greater than 150/90 mmHg at 6–9 AM and LVH had been determined by echocardiography (posterior wall thickness; PWT ≥ 12 mm). The patients were assigned to 2 groups at random and were given: guanabenz (GB; 2–8 mg at 11 PM, n = 17) or placebo (n = 17). Two years later, the average blood pressure of both groups as measured in the office was not significantly different: however, BP in the morning was significantly reduced from 158 ± 6 to 134 ± 4 mmHg in GB treated group (P < 0.001). In 14 of 17 patients in GB treated group, LVH resolved and there was only mild progression of nephropathy (serum creatinine: 1.69 ± 0.18 to 1.81 ± 0.19 mg/dl). In 12 of 14 patients in placebo group, whose morning blood pressure remained at greater than 150/90 mmHg, LVH was retained and there was moderate progression of nephropathy (serum creatinine: 1.73 ± 0.14 to 2.62 ± 0.50 mg/dl). From these results, it is suggested that antihypertensive treatment with combination therapy based on self-monitoring BP is cardio-renoprotective in patients with chronic renal insufficiency and LVH.     

Relationship Between Blood Pressure and Urinary Albumin Excretion Rate in Young Danish Type 1 Diabetic Patients: Comparison to Non-diabetic Children

In 1989 a nation-wide investigation of blood pressure and urinary albumin excretion rate (AER) was carried out in 506 boys and 441 girls with Type 1 diabetes (approximately 80 % of total) treated at 22 paediatric departments. In addition a reference population from 1979 consisting of 663 healthy non-diabetic children (334 boys, 329 girls) served as a control group with respect to blood pressure and body mass index. Microalbuminuria was defined as AER of 20–150 μg min^-1 in at least two out of three timed overnight urine collections and was diagnosed in 30 adolescents (16 boys, 14 girls). Five patients (3 boys, 2 girls) had overt proteinuria (AER: > 150μg min^-1). Age-related percentile charts based on one blood pressure reading were provided for normoalbuminuric diabetic patients and the healthy control group. The study revealed an increase in arterial blood pressure during the period of the pubertal growth spurt for the diabetic and non-diabetic group. The changes were most pronounced for systolic blood pressure. No statistically significant difference was observed in systolic and diastolic blood pressure between normoalbuminuric diabetic children and healthy control children. However, diabetic females aged 15–18 years had significantly higher diastolic blood pressure (75 ± 1 mmHg, n = 139, mean ± SE) than healthy control females (72± 1 mmHg, n = 155, p ± 0.01), and significantly (p ± 0.001) higher body mass index (diabetic females: 22.3± 0.2 kg m^-2 vs healthy females: 20.9± 0.2 kg m^-2, mean± SE). Boys aged from 15 to 18 years with Type 1 diabetes had significantly higher systolic blood pressure (123± 1 mmHg, n = 164) than girls (117± 1 mmHg, n = 139, p± 0.0001), while girls aged from 15 to 18 years had significantly higher diastolic blood pressure (75± 1 mmHg, n = 139) than boys (72± 1 mmHg, n = 72, p ± 0.01). Among the 30 adolescents with persistent microalbuminuria, 18 (10 boys, 8 girls) had diastolic blood pressure above the upper quartile for normoalbuminuric patients, while 2 out of 5 with macroalbuminuria had diastolic blood pressure above this limit. By multiple logistic regression the only risk determinants for elevated urinary albumin levels were age and diastolic blood pressure. These findings suggest that elevated arterial blood pressure is related to the increased prevalance of microalbuminuria observed in adolescents with Type 1 diabetes.     

The Effects of Natural Antioxidants from Tomato Extract in Treated but Uncontrolled Hypertensive Patients

Purpose  To evaluate the effect of adding tomato extract to the treatment regime of moderate hypertensives with uncontrolled blood pressure (BP) levels. Methods  Fifty four subjects with moderate HT treated with one or two antihypertensive drugs were recruited and 50 entered two double blind cross-over treatment periods of 6 weeks each, with standardized tomato extract or identical placebo. Plasma concentrations of lycopene, nitrite and nitrate were measured and correlated with BP changes. Results  There was a significant reduction of systolic BP after 6 weeks of tomato extract supplementation, from 145.8 ± 8.7 to 132.2 ± 8.6 mmHg (p < 0.001) and 140.4 ± 13.3 to 128.7 ± 10.4 mmHg (p < 0.001) in the two groups accordingly. Similarly, there was a decline in diastolic BP from 82.1 ± 7.2 to 77.9 ± 6.8 mmHg (p = 0.001) and from 80.1 ± 7.9 to 74.2 ± 8.5 mmHg (p = 0.001). There was no significant change in systolic and diastolic BP during the placebo period. Serum lycopene level increased from 0.11 ± 0.09 at baseline, to 0.30 ± 01.3 μmol/L after tomato extract therapy (p < 0.001). There was a significant correlation between systolic BP and lycopene levels (r = −0.49, p < 0.001). Conclusions  Tomato extract when added to patients treated with low doses of ACE inhibition, calcium channel blockers or their combination with low dose diuretics, had a clinically significant effect—reduction of BP by more than 10 mmHg systolic and more than 5 mmHg diastolic pressure. No side-effects to treatment were recorded and the compliance with treatment was high. The significant correlation between systolic blood pressure values and level of lycopene suggest the possibility of cause–effect relationships.     

The Relationship Between Obesity,Plasma Immunoreactive Insulin Concentration and Blood Pressure in Newly Diagnosed Indian Type 2 Diabetic Patients

The association of blood pressure with clinical and biochemical measures was studied in 185 newly diagnosed Type 2 diabetic patients, 74 impaired-glucose-tolerant (IGT) and 128 non-diabetic control subjects. Hyperglycaemic subjects were older than control subjects (controls 40 (24–59) years, IGT 48 (29–64) years, diabetic 43 (29–60) years, median (5th-95th centile) both p < 0.05). They were also more obese (body mass index (BMI) controls 23.5 kg m^?2 (17.2–29.9), IGT 26.0 kg m^?2 (19.8–33.9), diabetic 24.2 kg m^?2 (19.3–32.2)) and with a greater waist-hip ratio (controls 0.83 (0.70–0.98), IGT 0.88 (0.75–0.98), diabetic 0.89 (0.75–1.00)). Blood pressure was significantly higher in both IGT (systolic 127mmHg (108–162), diastolic 80 mmHg (66–99)) and diabetic patients (systolic 130 mmHg (104–160), diastolic 84 mmHg (66–102)) compared to non-diabetic controls (systolic 120 mmHg (100–151), diastolic 80 mmHg (60–94)). Univariate analysis showed that in diabetic patients systolic blood pressure was related to age (r = 0.17, p < 0.05), BMI (r= 0.23, p < 0.01) and plasma immunoreactive insulin (fasting and post glucose, r= ? 0.25, p<0.01) but not to C-peptide concentrations; diastolic blood pressure to BMI (r= 0.35, p < 0.001), waist-hip ratio (r = 0.23, p < 0.01) and plasma immunoreactive insulin (fasting r= 0.30, p < 0.001, post glucose r = ? 0.20, p < 0.05) but not to C-peptide concentrations. Multivariate analysis revealed that systolic blood pressure in diabetic patients was related to BMI (p < 0.01) and fasting immunoreactive insulin (p < 0.05) while diastolic blood pressure was related to BMI (p < 0.001) and waist-hip ratio (p < 0.01). Thus, blood pressure is associated with obesity even in our relatively non-obese population and it is also associated with plasma immunoreactive insulin concentrations. The mechanism of these associations remains to be established.     

Structural cardiac changes in relation to 24-h ambulatory blood pressure levels in borderline hypertension

Abstract. Objectives. To investigate left ventricular hypertrophy (LVH) in relation to 24-h ambulatory blood pressure (24-ABPM) and insulin levels in borderline hypertension. Design. A case-control study. Subjects. Borderline hypertensive men (diastolic blood pressure (DBP) 85–94 mmHg, n = 69) and age-matched normotensive controls (DBP ≤ 80 mmHg. n = 69) from a population screening programme. Main outcome measures. Echocardiography (M-mode). insulin (RIA) and 24-APBM (Del Mar P-IV) levels. Results. The borderline group showed a significant increase in septal thickness (10.4±1.5 vs. 9.7±1.5 mm. P < 0.01), peak systolic wall stress (218±38 vs. 202±38 10³ dynes cm^?2, P < 0.05) and a decrease in LV ejection time (28.4±2.5 vs. 29.5±2.1s, P < 0.01). The septum vs. posterior wall thickness ratio was significantly higher in the borderline group (1.13±0.14 vs. 1.06±0.14, P < 0.01). Casual BP levels did not correlate with LVH indices, while 24-ABPM systolic levels correlated strongly with LVH indices in the borderline group (r = 0.22–0.52, P < 0.05) but not in the normotensive group. Insulin levels correlates strongly with LVH indices in the normotensive group (r = 0.34–0.47, P < 0.01) but not the borderline, group. Conclusions. Signs of asymmetric LVH and altered ventricular function are already detectable in borderline hypertension. The data also suggest that early structural cardiac changes are related to ambulatory blood pressure profile, but not to casual blood pressure or trophic factors such as insulin.     

N-Acetylcysteine Antagonizes the Development But Does Not Reverse ACTH-Induced Hypertension in the Rat

We investigated the effect of antioxidant N-acetylcysteine (NAC) on adrenocorticotropic hormone (ACTH)-hypertension. Male Sprague-Dawley rats received NAC (10 mg/L) or water 4 days before ACTH/saline treatment for 13 days (prevention study). In a reversal study, NAC commenced on day 8 of ACTH/saline treatment and continued for 5 days. ACTH increased systolic blood pressure (SBP) in water drinking rats (111 ± 1 to 131 ± 3 mmHg, p < 0.001). In the prevention study, NAC + ACTH increased SBP (108 ± 2 to 120 ± 2 mmHg, p < 0.001) but less than ACTH alone (p′ < 0.05). In the reversal study, NAC had no significant effect (132 ± 4 to 124 ± 3 mmHg, ns). Thus, NAC partially prevented but did not reverse ACTH-induced hypertension.     

Modulation of Nitric Oxide Synthase Activity in Brain,Liver, and Blood Vessels of Spontaneously Hypertensive Rats by Ascorbic Acid: Protection from Free Radical Injury

End organ damage in essential hypertension has been linked to increased oxygen free radical generation, reduced antioxidant defense, and/or attenuation of nitric oxide synthase (NOS) activity. Ascorbic acid (AA), a water-soluble antioxidant, has been reported as a strong defense against free radicals in both aqueous and nonaqueous environment. In this study we examined the hypothesis that antioxidant ascorbic acid may confer protection from increased free radical activity in brain, liver, and blood vessels of spontaneously hypertensive rats (SHR). Male SHRs were divided into groups: SHR + AA (treated with AA, 1 mg/rat/day; for 12 weeks) or SHR (untreated). Wister-Kyoto rats (WKY) served as the control. Mean systolic blood pressure (SBP) in treated and untreated SHR was 145 ± 7 mmHg and 142 ± 8 mmHg, respectively. AA treatment prevented the increase in systolic blood pressure in SHR by 37 ± 1% (p < 0.05). NOS activity in the brain, liver, and blood vessels of WKY rat was 1.82 ± 0.02, 0.14 ± 0.003, and 1.54 ± 0.06 pmol citruline/mg protein, respectively. In SHR, total NOS activity was significantly reduced by 52 ± 1%, 21 ± 3%, and 44 ± 4%, respectively. AA increased NOS activity in brain, liver, and blood vessels of SHR from 0.87 ±.03, 0.11 ±.01, and 0.87 ±.08 pmol citruline/mg protein to 0.93 ± 0.01, 0.13 ± 0.001, and 1.11 ± 0.03 pmol citruline/mg protein (p < 0.05), respectively. Lipid peroxides in the brain, liver, and blood vessels from WKY rats were 0.87 ± 0.06, 0.11 ± 0.005, and 0.47 ± 0.04 nmol MDA equiv/mg protein, respectively. In SHR, lipid peroxides in brain, liver, and blood vessels were significantly increased by 40 ± 3%, 64 ± 3%, and 104 ± 13%, respectively. AA reduced lipid peroxidation in liver and blood vessels by 17 ± 1% and 34 ± 3% but not in brain. Plasma lipid peroxides were almost doubled in SHR (p < 0.01) together with a reduction in total antioxidant status (6 ± 0.1%; p < 0.05), nitrite (53 ± 2%; p < 0.05) and superoxide dismutase (SOD) activity (36 ± 2%; p < 0.05). AA treatment reduced plasma lipid peroxide (p < 0.001), and increased TAS (p < 0.001), nitrite (p < 0.001), and SOD activity (p < 0.001). From this study, we conclude that brain, liver, and blood vessels in SHR are susceptible to free radical injury, which reduces the availability of NO either by scavenging it or by reducing its production via inhibiting NOS. In addition, brain, liver, and blood vessels in SHR; may be protected by antioxidant, which improves total antioxidant status, and SOD thus may prevent high blood pressure and its complications.     

Night Blood Pressure: Relation to Organ Lesions in Microalbuminuric Type 1 Diabetic Patients

Ambulatory blood pressure was measured in 23 microalbuminuric Type 1 diabetic patients without hypertension. Nine patients had a reduction in mean arterial blood (MAP) pressure at night < 10% of their day-time value (non-dippers). The following parameters were measured: glomerular filtration rate (GFR), overnight urinary excretion of albumin (UAE), sodium and potassium, left ventricular dimensions, extracellular volume (ECV), plasma aldosterone, and arginine vasopressin (AVP). Night-time MAP was 11 mmHg lower in patients designated as dippers than in non-dippers. Day-time MAP was similar in dippers (98 ± 5 mmHg) and non-dippers (99 ± 8 mmHg, NS). No statistical significant difference was found for UAE in dippers (geometric mean, x/– tolerance factor, μg min^-1) (72 x/– 2.1) vs non-dippers (63 x/– 2.1), for left ventricular mass index (63 ± 12 vs 59 ± 10 g m^-2), or for GFR (134 ± 19 vs 148 ± 22 ml min^-1). Aldosterone and AVP were lower in non-dippers (p < 0.05) and a negative correlation in all patients was noticed between ECV and aldosterone (rho = ?0.50, p < 0.05). Sodium and potassium excretion and ECV were indistinguishable between the groups. We conclude (1) that impaired reduction of night blood pressure does not seem to be associated with more signs of renal or cardiac lesions and (2) that the lower aldosterone and AVP in non-dippers may counteract volume expansion.