Cardiovascular status after postural change in compensated cirrhosis: an argument for vasodilatory concept

Abstract: It seems that hypervolemia and vasodilatation coincide in compensated cirrhosis, but neither rank nor importance of these factors has been fully clarified in adaptive response to postural change. We studied, with gated equilibrium radionuclide angiography and thoracic electrical bioimpedance the hemodynamic status of 19 patients with compensated cirrhosis and 18 healthy subjects in upright and supine positions. In the upright position, the cirrhotic patients were hypotensive and had decreased peripheral vascular resistance despite increased cardiac output. The transition to the supine position was accompanied by a significant fall in the heart rate and an increase in the stroke volume in both controls (92±22 to 63±10 beats/min, and 38±9 to 62±19 ml/m², respectively) and cirrhotic patients (101±20 to 79±13 beats/min, and 44±15 to 63±19 ml/m², respectively). Besides, the diastolic arterial pressure fell in controls from 89±9 mmHg to 81 ± 11 mmHg; p <0.01, while it remained unchanged in cirrhotic patients (77±17 vs 82±13 mmHg). In the supine position, the cirrhotic patients presented tachycardia and left ventricular hyperkinesy (increased velocity of left ventricular filling and emptying). In conclusion, these results show that in compensated cirrhosis the decreased arterial tone and peripheral blood pooling are important factors of adaptive hemodynamic reaction to postural change.     

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.     

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.     

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.     

The Effect of Sodium Depletion and Potassium Supplementation on Vasopressin,Renin and Catecholamines in Hypertensive Men

ABSTRACT Seventeen 50-year-old hypertensive men (157±4/110±2 mmHg, mean ± SE) were given low sodium diet for one week, which was supplemented with potassium the following week. The urinary Na⁺/K⁺ excretion ratio changed from 2:1 to 1:5 and 1:12, respectively, during dietary intervention. Arterial plasma vasopressin decreased by 3.4±1.7 ng/l (0.05>p<0.10) and urinary excretion of vasopressin was reduced by nearly 50% (p<0.001) during sodium depletion, while plasma noradrenaline increased by 38% (p<0.001) and plasma dopamine showed an increase by 58% (p<0.001). Plasma renin concentration increased four-fold during sodium depletion (p<0.001). With combined salt depletion and potassium supplementation, arterial plasma vasopressin decreased by 9.5±4.0 ng/l (p<0.05) compared to control. Urinary excretion of vasopressin together with plasma noradrenaline and dopamine were unchanged during the second week. The reduction of blood pressure was most marked during the first week (143±3/103±2 mmHg, p<0.05), but continued to fall also during the second week. Thus, during sodium restriction in middle-aged hypertensive men, blood pressure reduction occurs concomitantly with inhibited vasopressin release, despite enhanced renin and catecholamine release. Potassium supplementation during sodium restriction induces only minor changes in these variables.     

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     

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.     

Effects of Neuropeptide Y on Cardiac Performance and Renal Blood Flow in Conscious Normotensive and Renal Hypertensive Rabbits

The effects of neuropeptide Y (NPY, 10 ug/kg bolus iv) on cardiac output, renal blood flow and myocardial contractility were determined in intact renal hypertensive and normotensive rabbits instrumented with ultrasonic flow transducers or left ventricular catheters.

The basal plasma concentration of NPY-like immunoreactivity in arterial blood was greater in the hypertensive rabbits (4.2 ± 0.7 ug/1) than in normotensive animals (2.2 ± 0.4 ug/l, p < 0.05). There were similar moderate increases in arterial blood pressure and total peripheral resistance following NPY, but a small NPY-induced reduction in cardiac output in normotensive rabbits was not seen in hypertensive animals. Resting peak left ventricular dP/dt (an index of myocardial contractility) was higher in hypertensive rabbits (73972 ± 619 vs 5551 ± 2342 mmHg/sec, p < 0.05), but there was no significant difference between the maximum NPY-induced falls in peak dP/dt.

NPY produced significant peak reductions in renal blood flow in both hypertensive (from 2.5 ± 0.2 to 1.22 ± 0.2 kHz, p < 0.05) and in normotensive rabbit groups (from 2.2 ± 0.1 to 0.3 ± 0.1 kHz, p<0.05), but the fall in renal blood flow and the corresponding rise in renovascular resistance were smaller in the hypertensive animals (p < .0 5). The cause of this apparent decrease in renovascular reactivity in the renal hypertensive model was not determined.     

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 cross-over 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 140/90 mmHg. 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 ± 3 mmHg, p < 0.01; 129 ± 3 vs. 134 ± 4, p < 0.05). Trough to peak ratio 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.     

Prolonged Anti-Hypertensive Effects of Oral Sitaxsentan, a Selective ETA Endothelin Receptor Antagonist, in Spontaneoulsy Hypertensive Hamsters

Introduction The purpose of this study was to determine whether prolonged oral therapy with sitaxsentan, a potent selective ET_A endothelin receptor antagonist, normalizes systolic blood pressure in spontaneously hypertensive hamsters, a new rodent model of high-renin genetic hypertension. Materials and Methods Spontaneously hypertensive hamsters received either oral sitaxsentan (15 mg kg⁻¹ day⁻¹) dissolved in high purity water or saline for 7 weeks. Systolic blood pressure was monitored in lightly anesthetized animals using the leg-cuff method. Results We found that sitaxsentan elicited a significant decrease in systolic blood pressure in spontaneously hypertensive hamsters from 175 ± 6 mmHg at baseline to 109 ± 7 mmHg after 7 weeks (p < 0.05). Although treatment of spontaneously hypertensive hamsters with saline was also associated with a significant decrease in systolic blood pressure from baseline, the magnitude of response was significantly less than that observed with sitaxsentan (p < 0.05). Discussion Collectively, these proof-of-principle data indicate that prolonged oral sitaxsentan therapy normalizes systolic blood pressure in spontaneously hypertensive hamsters. We suggest that selective ET_A endothelin receptor blockade could be beneficial in the treatment of essential hypertension associated with high renin plasma levels.     

Measurement of intravariceal pressure by fine needle direct puncture in hepatitis B surface antigen-positive cirrhotic patients: The effect of vasopressin

The pressure of oesophageal varices was determined by fine needle direct puncture in 19 patients with hepatitis B surface antigen (HBsAg)-positive cirrhosis after the first episode of variceal bleeding before endoscopic sclerotherapy. Both the stability and reliability of the measurement of intravariceal pressure by fine needle puncture were confirmed. Seven patients received intravenous 1 mL normal saline. Intravariceal pressure did not change before and after injection of normal saline (16.3 ± 4.0 vs 16.0 ± 4.0 mmHg, P > 0.05). Twelve patients received intravenous 1 units vasopressin and this caused a significant reduction in intravariceal pressure (15.6 ± 2.6 vs 10.3 ± 2.9 mmHg, P lt; 0.0001). The average basal intravariceal pressure in these patients was 15.8 ± 3.1 mmHg. After intravariceal pressure was recorded, the needle was left in situ and endoscopic sclerotherapy commenced immediately. During the investigation, no adverse reaction or complication was encountered. It was concluded that the measurement of intravariceal pressure by fine needle direct puncture followed by immediate sclerotherapy is a safe and simple method to evaluate the short-term effect of drug prevention from oesophageal variceal bleeding and that vasopressin causes reduction of intravariceal pressure.     

Effect of Correction of Hyperglycemia on Left Ventricular Function in Non-Insulin-Dependent (Type 2) Diabetics

ABSTRACT Systolic time intervals (STI) were recorded in 33 newly diagnosed non-insulin-dependent diabetics (19 men, 14 women, aged 44–64 years) before and after 3–8 months' dietary therapy. The mean (±SD) fasting blood glucose was 11.1±2.6 mmol/l before treatment and 7.8±1.8 at the second examination (p<0.001). Concomitantly with the decline in blood glucose concentration, the heart rate corrected pre-ejection period (PEP) decreased from 139±11.9 to 135±14.4 msec (mean±SD) (p<0.05), the heart rate corrected left ventricular ejection time (LVET) increased from 400 ± 15.1 to 410±20.7 msec (p<0.0025) and the PEP/LVET ratio decreased from 0.39±0.06 to 0.36±0.06 (p<0.005). When the diabetics were divided into two groups according to the degree of the decline in blood glucose concentration, only those whose fasting blood glucose decreased by ≥3 mmol/l showed significant changes in STI. No significant changes were observed in the mean heart rate or systolic blood pressure during the treatment. Cardiac dysfunction occurring in untreated non-insulin-dependent diabetics may be caused by metabolic factors and it may be reversed at least partially by correction of hyperglycemia.     

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.     

Acute effects of hemodialysis on echographic-determined cardiac performance: Improved contractility resulting from serum increased calcium with reduced potassium despite hypovolemic-reduced cardiac output

The hemodialysis session leads to reduction in circulating blood volume (TBV) and arterial pressure (BP) plus correction of electrolyte imbalance. The effect of these alterations on cardiac performance was evaluated in 18 patients with end-stage renal disease. Hemodialysis for 5 hours led to significant reduction (p < 0.001) in weight, TBV, and BP. Neither ejection fraction nor percentage fiber shortening was altered, whereas mean velocity of circumferential fiber shortening (mean V_CF) and mean systolic ejection rate (MSER) were both significantly increased (1.17 ± 0.20 to 1.38 ± 0.28 circ/sec and 2.38 ± 0.27 to 2.80 ± 0.40 EDV/sec, respectively; p < 0.001 for each). Since both venous return and systolic BP were decreased, increase in velocity of ventricular contraction implies enhancement of cardiac performance beyond what would be expected from alterations in ventricular filling and resistance to ejection. This enhancement is possibly related to concomitant reduction in serum potassium (p < 0.001) and increase in serum calcium (p < 0.005) achieved by hemodialysis.     

Puerarin protects against endothelial dysfunction and end-organ damage in Ang II-induced hypertension

Puerarin, a major isoflavonoid compound from Chinese herb Kudzu roots, has been widely used for the treatment of hypertensive and cardiovascular diseases in China. Here, we investigated puerarin’s beneficial effects on the cardiovascular system in angiotensin (Ang) II-induced hypertensive rats. Sprague–Dawley rats were treated with Ang II for 5 days or with puerarin for 10 days followed by Ang II and puerarin for 5 days. Endothelium-dependent relaxation (EDR) to acetylcholine was determined using an organ chamber bath. Ang II increased the systolic blood pressure (SBP: 178 ± 5 mmHg vs. 112 ± 3 mmHg in control, p < 0.05), aortic (30%, p < 0.05), and left ventricular (LV) weight (23%); puerarin reduced SBP (160 ± 2 mmHg, p < 0.05), aortic, and left ventricular weight in Ang II-infused rats. Puerarin also reduced aortic medial thickness and myocardial cell surface area in Ang II-infused rats. Compared with control rats, Ang II infused rats exhibited an impaired EDR with reduction in the protein expression of phosphor-eNOS at Ser 1177 and an increase in the expression of gp91phox (85%), p22phox (113%), transforming growth factor β1 (145%) and vascular cell adhesion molecule 1 (82%). Puerarin improved EDR and reversed the changes in Ang II-induced protein expression of above molecules. Our results demonstrate that in Ang II-induced hypertensive rats, puerarin protects against endothelial dysfunction and end organ damage with a mild reduction in SBP, and that the cardiovascular beneficial effects of puerarin may be in part attributed to its anti-oxidant and upregulation of phosphor-eNOS.     

In vivo and in vitro models to test the hypothesis of particle-induced effects on cardiac function and arrhythmias

Exposure to ultrafine particles (UFPs) by inhalation increases the number and severity of cardiac events. The specific mechanism(s), of action are unknown. This study was designed to examine whether UFPs could exert a direct effect on the cardiovascular system without dependence upon lung-mediated responses. The direct effects of UFPs were determined in normal rats (infused intravenously with UFPs), and in the isolated Langendorff perfused rat heart. UFPs from either ambient air (UFAAs) or diesel engine exhaust (UFDGs) were studied. Infusion of UFDGs prepared in our laboratory caused ventricular premature beats (VPBs) in 2 of 3 rats in vivo. Ejection fraction in creased slightly (∼4.5%) in rats receiving UFPAA and was unchanged in the UFDG and saline groups in vivo. In the isolated rat heart, perfused according to Langendorff, UFDGs caused a marked ncrease in left-ventricular end-diastolic pressure (LVEDP; from 12.0±4.6 mmHg to 24.8±11.2 mmHg, p<0.05) after 30 min of exposure. UFPs isolated from industrial diesel particulate matter (UFIDs), obtained from the National Institute of Standards and Technology, caused a significant decrease in left-ventricular systolic pressure (LVSP; from 85.7±4.0 mmHg to 37.9±20.3 mmHg, p<0.05) and ±dp/dt (from 2365±158 mmHg/s to 1188±858 mmHg/s, p<0.05) at 30 min after the start of infusion. This effect was absent when the soluble fraction (containing no particles) isolated from the UFIDs was studied. These findings indicate that UFPs can have direct effects on the cardiovascular system that are independent of effects of particles on the lungs.     

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.     

EFFECT OF NITRIC OXIDE INHIBITION ON KIDNEY FUNCTION IN EXPERIMENTAL RENOVASCULAR HYPERTENSION

We examined the effect of acute systemic blockade of nitric oxide (N0) synthesis on blood pressure and renal function in rats with angiotensin II dependent two-kidney, one-clip Goldblatt hypertension. Hypertensive animals had significantly higher blood pressures, plasma NO metabolite concentrations and urinary NO metabolite excretion rates than control rats. Intravenous administration of N^G-nitro-L-arginine methylester (L-NAME) (10 mg/kg) increased mean arterial pressure in both hypertensive and control animals with the magnitude of increase being greater in hypertensive than control rats (32±3 vs. 20±2 mmHg,p< 0.05). L-NAME did not affect glomerular filtration rates of normal and clipped kidneys but significantly decreased non-clipped kidney glomerular filtration rate (1.1±0.1 vs. 0.7±0.1 ml/min per g kidney wt, p< 0.05). Blood flow to normal and non-clipped kidneys fell in response to L-NAME. Percent reduction in renal blood flow produced by L-NAME was significantly greater in non-clipped than normal kidneys (38±3 vs. 24±2%,p< 0.05). In contrast, clipped kidney blood flow increased after L-NAME (3.3±0.2 vs. 4.0±0.2 ml/min per g kidney wt,p< 0.05). An identical improvement in clipped kidney blood flow occurred when arterial pressure was raised with aortic constriction indicating that the systemic pressor effect of L-NAME was responsible for this finding. These results indicate that NO plays an important role in systemic and non-clipped kidney hemodynamics in renovascular hypertension. Because NO has little influence on stenotic kidney function, the stimulus for increased NO system activity in this disease appears to be vascular shear stress rather than elevated circulating or intrarenal angiotensin II concentrations.     

Effect of stent implantation on blood pressure control in adults with coarctation of the aorta

BackgroundStenting of coarctation of the aorta (CoA) generally results in good angiographic results and a decrease in transcoarctation pressure gradient. However, effect on blood pressure control is less clear. The goal of the current retrospective analysis was to investigate the effects of CoA stenting on blood pressure control.MethodsA retrospective analysis was conducted in consecutive adult patients with a CoA who underwent a percutaneous intervention at one of the three participating hospitals. Measurements included office blood pressure, invasive peak-to-peak systolic pressure over the CoA, diameter of the intima lumen at the narrowest part of the CoA and use of medication. The follow-up data were obtained, based on the most recent examination date.ResultsThere were 26 native CoA and 17 recurrent CoAs (total n = 43). Seven of them underwent two procedures. Mean peak-to-peak gradient decreased from 27 mmHg to 3 mmHg (p < 0.001), and minimal diameter increased from a mean of 11 mm to 18 mm (p < 0.001). Mean systolic blood pressure decreased from 151 ± 18 mmHg to 135 ± 19 mmHg at first follow-up of 3.8 ± 1.9 months and 137 ± 22 mmHg at latest follow-up of 19.5 ± 10.9 months (p = 0.001 and p = 0.009, compared to baseline, respectively). The total number of hypertensive patients decreased from 74% to 27% at latest follow-up. No significant change in antihypertensive medication was observed.ConclusionA clinically significant decrease in systolic blood pressure of approximately 16 mmHg was shown after (re)intervention in CoA patients, which sustained at follow-up. This sustained decrease of blood pressure can be expected to lead to less future adverse cardiovascular events.     

Effects of morphine and aminophylline on the severity of obstruction to left ventricular outflow in idiopathic hypertrophic subaortic stenosis: potential adverse effects in treatment of pulmonary edema

Although morphine sulfate and aminophylline are commonly employed in the management of acute pulmonary edema of diverse etiologies including idiopathic hypertrophic subaortic stenosis (IHSS), the effects of morphine and aminophylline on left ventricular (LV) outflow obstruction in IHSS are unknown. Thus to determine the actions of morphine and aminophylline in IHSS, seven patients with IHSS (mean peak resting systolic gradient 16 mmHg, mean Valsalva provoked gradient 87 mmHg) received 5 mg morphine intravenously and simultaneous LV and brachial arterial pressures were continously monitored and cardiac outputs obtained. On return to control hemodynamics, 250 mg aminophylline was infused in three patients and hemodynamics repeated. Peak increase in gradient with morphine occurred in 5 min in each patient and average maximal gradient was 48 mmHg (p<0.001). Peak LV systolic pressure increased 158 to 182 mmHg (p<0.05); LV end-diastolic pressure declined 12 to 8 mmHg (p<0.005); cardiac index decreased 3.18 to 2.89 l/min/m² (p<0.005); while heart rate and total systemic vascular resistance were unchanged (p>0.05). Aminophylline increased peak gradient to 57 mmHg; lowered LV end-diastolic pressure by 2 mmHg; decreased total systemic vascular resistance 1610 to 1120 dyne s · cm^?5; while cardiac index was unchanged. Therefore morphine and aminophylline can rapidly increase LV outflow obstruction to marked extents in IHSS. These data indicate morphine worsens subaortic stenosis by decrease in LV preload through systemic venodilation, whereas aminophylline increases intraventricular gradient predominantly by peripheral arterial dilation. Thus morphine and aminophylline should be avoided, or used cautiously in low doses, in management of acute pulmonary edema in IHSS.