Handgrip Increases Endothelin-1 Secretion in Normotensive Young Male Offspring of Hypertensive Parents

Objectives. We tested the hypothesis that an abnormal response of plasma endothelin-1 (ET-1) is elicited by handgrip exercise (HG) in young normotensive offspring of hypertensive parents.Background. It has been hypothesized that ET-1 is involved in blood pressure control and plays a pathophysiologic role in the development of clinical hypertension.Methods. Two groups of healthy male subjects, 11 with hypertensive parents (group A) and 10 without a family history of hypertension (group B), underwent 4 min of HG at 50% maximal capacity. Heart rate and blood pressure and plasma levels of ET-1, epinephrine and norepinephrine were measured at baseline, peak HG, and after 2 (R2) and 10 (R10) min of recovery.Results. Group A had higher norepinephrine levels than group B throughout the test (baseline 181 ± 32 [SEM] vs. 96 ± 12 pg/ml, p < 0.05; peak HG 467 ± 45 vs. 158 ± 12 pg/ml, p < 0.000001; R2 293 ± 46 vs. 134 ± 8 pg/ml, p < 0.01; R10 214 ± 27 vs. 129 ± 10 pg/ml, p < 0.0005); no significant difference in epinephrine levels was detected. Compared with group B subjects, group A had higher baseline ET-1 levels (1.07 ± 0.14 vs. 0.59 ± 0.11 pg/ml, p < 0.02), which increased to a greater extent at peak HG (1.88 ± 0.31 vs. 0.76 ± 0.09 pg/ml, p < 0.005) and R2 (2.46 ± 0.57 vs. 1.31 ± 0.23 pg/ml, p < 0.05) and remained elevated at R10 (3.16 ± 0.78 vs. 0.52 ± 0.09 pg/ml, p < 0.002). Multivariate analysis demonstrated that only a family history of hypertension (chi-square = 7.59, p = 0.0059) and ET-1 changes during HG (chi-square = 4.23, p = 0.0398) were predictive of blood pressure response to HG and that epinephrine and norepinephrine were not.Conclusions. The response to HG in offspring of hypertensive parents produced increased ET-1 plasma levels and resulted in a sustained ET-1 release into the bloodstream during recovery compared with offspring of normotensive parents. This may be an important marker for future clinical hypertension.     

Abnormalities of Anthropometric,Hemodynamic, and Autonomic Variables in Offspring of Hypertensive Parents

Young adult offspring of hypertensive parents (pHTN⊕) are a good model for assessing abnormalities of anthropometric, cardiometabolic, and autonomic variables prior to clinical hypertension. The objectives of this study were to determine whether these variables and autonomic responses to oral carbohydrates were altered in offspring of pHTN⊕. Two hundred consecutive patients, including 100 pHTN⊕, were evaluated, with 29 patients, including 14 pHTN⊕, given a 70‐gram carbohydrate load. The pHTN⊕ group had higher blood pressure, pulse pressure, abdominal circumference (AC), weight, body mass index, and basal metabolic rate than offspring of normotensive parents (pHTN∅). At baseline, the low‐frequency (LF, sympathetic) to high‐frequency (HF, parasympathetic) ratio, assessed by spectral analysis of heart rate variability, was similar in both groups. After the carbohydrate load, the LF/HF ratio was greater in offspring of pHTN⊕. pHTN⊕ individuals have abnormalities of anthropometric and hemodynamic variables at baseline and autonomic responses to oral carbohydrates before developing hypertension.

Hypertension is associated with a large and growing health and economic burden of cardiovascular and renal diseases.¹, ² High arterial pressure causes target organ changes in the brain, heart, vessels, and kidneys. The etiology of arterial hypertension is unknown in most cases, although genetic factors play an important role.³ Environmental and behavioral factors also participate and include excessive salt and alcohol intake, stress, smoking, sedentary lifestyle, and obesity. Obesity is commonly associated with hypertension and appears to begin early in offspring of hypertensive parents (pHTN⊕).⁴, ⁵ The offspring of pHTN⊕ are more likely to develop hypertension than those of normotensive parents (pHTN∅).⁴ Normotensive offspring of pHTN⊕ have higher casual arterial pressure than normotensive offspring of pHTN∅.⁴ The difference in arterial pressure between children of pHTN∅ and children of pHTN⊕ has been reported in infancy, childhood, adolescence, and adulthood.⁶ Anthropometric data such as body mass index (BMI), waist circumference, and neck circumference might be related to the pathogenesis of hypertension in the offspring of pHTN⊕. However, there is no consensus regarding this issue.⁷, ⁸, ⁹ The interrelation between offspring of pHTN⊕ and both anthropometric and environmental variables can result in increased blood pressure (BP) in patients with familial predisposition, ie, gene‐environment interactions.¹⁰ Although associations between hypertension and anthropometric, metabolic, and autonomic nervous system variables were reported,¹¹, ¹², ¹³ few studies have addressed this association in offspring of pHTN⊕ parents.The sympathetic nervous system plays an important role in the pathogenesis of arterial hypertension. Greater activity of the sympathetic nervous system leads to lower heart rate variability (HRV) and higher risk for cardiovascular events, such as myocardial infarction and sudden death.¹⁴, ¹⁵ Conversely, higher parasympathetic nervous system activity increases HRV and is associated with lower heart‐related mortality. Autonomic nervous system regulation in hypertensive patients appears to be altered, and the changes can be detected through spectral analysis.¹⁵ Autonomic nervous system changes can be affected by environmental factors including food intake, and may be modulated by family history. Inappropriate increase in sympathetic activity after any kind of challenge in normotensive patients could be indicative of autonomic imbalance preceding the onset of hypertension. In one report, normotensive offspring of pHTN⊕ show increased sympathetic activity at baseline and after isometric exercise.¹⁶ Carbohydrate consumption can have a negative effect on sympathetic activity in hypertensive patients.¹⁷ However, the impact of carbohydrate ingestion on autonomic balance has not been reported in normotensive offspring of pHTN⊕.The aim of this study was to assess anthropometric, hemodynamic, and metabolic variables, including basal metabolic rate, in pHTN⊕ and pHTN∅ offspring prior to the onset of hypertension. In a subset of pHTN⊕ and pHTN∅ offspring, autonomic function was assessed under fasting conditions and following an oral carbohydrate load.     

Nebivolol in Obese and Non-Obese Hypertensive Patients

Use of β-blockers in hypertensive obese patients remains controversial because of concerns about potential influences on weight, lipids, and glucose metabolism. The authors examined a pooled analysis of 3 multicenter randomized placebo-controlled trials. Patients were randomized to placebo or an increasing dose of nebivolol for 12 weeks. Primary outcome was the mean baseline to end point change in trough mean sitting diastolic blood pressure (SiDBP). Secondary outcomes were baseline to end point changes in trough sitting systolic blood pressure (SiSBP); trough standing and peak supine diastolic blood pressure and systolic blood pressure. Nebivolol reduced SiDBP significantly compared with placebo at all doses ≥2.5 mg in obese and non-obese patients. Reductions in SiSBP with nebivolol were higher than controls at all studied doses ≥5 mg in non-obese and ≥2.5 mg in obese patients. These findings and nebivolol's neutral effects on lipid and carbohydrate metabolism suggest that it is one option for blood pressure control in the moderately obese population.     

The Bergen Blood Pressure Study: Sodium Intake and Ambulatory Blood Pressure in Offspring of Hypertensive and Normotensive Families

Sodium intake, estimated by the 24-h urine sodium excretion, was assessed in 39 offspring of hypertensive families and 37 offspring of normotensive families. The family history of hypertension or normotension was defined according to parental BP data from two surveys conducted 27 years apart. Urine sodium excretion was similar in offspring of hypertensive and normotensive families, averaging 136 and 137 mmol/24 h, respectively. Monitored by non-invasive methodology in the urine sampling period, the average 24-h ambulatory blood pressure (BP) was approximately 10/10 mmHg higher in offspring of hypertensive than normotensive families. The clinically and statistically significant differences in BP between groups could not be explained by differences in sodium intake. After adjustment for confounding variables, the BP was not associated with the sodium excretion in the material as a whole or in either offspring group.     

Aortic Distensibility in Normotensive, Untreated and Treated Hypertensive Patients

Background: Compared with normotensive subjects, untreated hypertensive patients show a decrease of their aortic distensibility. Whether antihypertensive treatment, by reducing blood pressure and changing functional and/or structural abnormalities of the arterial wall, may prevent or reverse the arterial damage due to the accelerated ageing process remains unclear. The objective of the present study was to determine, using a cross-sectional approach, whether aortic distensibility as measured by pulse wave velocity, in treated hypertensive patients whose diastolic blood pressure had been normalised for several months, was significantly improved over that of untreated hypertensive patients.

Methods: Carotid femoral pulse wave velocity was measured in 124 normotensive subjects and 388 hypertensive patients. The latter group included 164 treated patients with well controlled diastolic blood pressure and 224 untreated hypertensive subjects. The three groups did not differ in other cardiovascular risk factors.

Results: In each group there was a significant relationship between age and pulse wave velocity. When compared with untreated hypertensives, treated hypertensives with well controlled diastolic blood pressure had significantly lower blood pressure and pulse wave velocity according to age. However, although diastolic blood pressure of well controlled hypertensives was not significantly different from that of normotensive subjects, the aortic distensibility of the controlled hypertensives remained reduced showing two characteristics: a faster increase in pulse wave velocity with age and a negative relationship with HDL-cholesterol.

Conclusion: These results suggest that long-term antihypertensive treatment and control of blood pressure using only diastolic blood pressure criteria may not fully reverse arterial alteration associated with hypertensive vascular disease.     

Effects of Psychological and Physical Covariates on Plasma Catecholamines in Borderline Hypertensives and Offspring of Hypertensive Parents

The interpretation of plasma catecholamine measurements may be influenced by psychological and physical factors. Therefore, catecholamine concentrations were adjusted for between-subject differences by the following possible confounding factors, i.e. body-mass index, individual maximal physical work capacity, urinary sodium excretion rates and anxiety score. Subjects were 24 borderline essential hypertensives, aged 18–24 years, 50 age-matched normotensive offspring of hypertensive parents and 49 controls with no family history of hypertension studied at rest and during mental stressors (Stroop colour-word conflict test, mental arithmetic). Borderline hypertensives had consistently higher adjusted venous noradrenaline concentrations than control subjects (p<0.05). Adjusted plasma adrenaline concentrations were higher in borderline hypertensive subjects than in offspring of hypertensive parents during supine rest. Despite its limitations, venous plasma noradrenaline concentrations when adjusted for work capacity, body-mass, sodium excretion and anxiety suggest enhanced sympatho-neural activity in young borderline essential hypertensives.     

3H-Naloxone Binding in Brain Regions of Normotensive Wistar, Spontaneously Hypertensive and Renal Hypertensive Rats

In order to study the role of opioid receptors in two models of experimental hypertension the binding of ³H-naloxone to membranes prepared from discrete brain regions and spinal cord was determined. Renal hypertensive rats (RHR) were found to have a greater density of ³H-naloxone binding sites in the hippocampus and hypothalamus when compared to spontaneously hypertensive rats (SHR) and normotensive Wistar rats (NR). The apparent dissociation constant (K_d) for ³H-naloxone binding did not differ between groups.     

Prostaglandins,Catecholamines, Renin and Aldosterone During Hypertensive and Normotensive Pregnancy

Urinary excretion of prostaglandin E² (PGE²) and F²α (PGF²α), plasma concentrations of renin (PRC), aldosterone (PAC), noradrenaline (PNA) and adrenaline (PA) were determined in the third trimester of pregnancy, 5 days and 3 months after delivery in preeclampsia and normotensive pregnant and non-pregnant control subjects. PGE² was higher in pregnant control subjects than in non-pregnant subjects, but reduced to non-pregnant level in preeclampsia. PGF²α was the same in preeclampsia and normotensive pregnancy but higher than in the non-pregnant group. PRC and PAC were increased during pregnancy, but considerably lesser in preeclampsia than during normotensive pregnancy. PNA and PA were the same in all three groups. All parameters were normal 3 months after delivery. There were no correlations between any of the hormones and blood pressure in any of the groups. PGE²was positively correlated to PRC. The lack of renal PGE²in preeclampsia might be responsible for the decrease in renal blood flow and sodium excretion, and the changes in PRC and PAC are supposed to be secondary to changes in PGE². It is hypothesised that preeclampsia is a state of prostaglandin deficiency.     

Salt Preferences of Normotensive and Hypertensive Older Individuals

The aim of this study was to evaluate the preference for salt in hypertensive and normotensive older individuals. Hypertensive (group 1: n=32, aged 73.7±6.3 years) or normotensive patients (group 2: n=26, aged 71.5±8.0 years) were submitted to a test to determine their preference for bread samples with different salt concentrations: 1.5%, 2.0% (usual concentration), and 2.7%, and were reevaluated 2 weeks later using the same salt concentrations, but with the addition of oregano. Twenty‐four–hour urinary sodium excretion (UNaV), blood pressure (BP), and body mass index (BMI) were obtained. Systolic BP, BMI, and UNaV were higher in group 1. In the first analysis, group 1 showed greater preference for the saltiest sample (P=.001). Comparing the first evaluation and the second, a greater preference for less salty samples was observed in both groups (P<.01). Hypertensive older patients consumed more salt and showed a greater salt preference than the normotensive patients. The use of the spice reduced the preference for salt in both groups.     

高胰岛素血症加重高血压病人的靶器官损害

对 14 0例高血压 (HT )病人进行口服葡萄糖耐量试验(OGTT)和胰岛素释放试验 (IRT )。每个病人进行心、脑、肾检查 ,包括超声心动图、2 4h动态心电图、脑 SPECT、CT检查、2 4h尿白蛋白定量、内生肌酐清除率、血、尿β2 -微球蛋白。分为 3组 :1组 ,H T并正常 OGTT和 IRT(n=2 7,19.3% ) ;2组 ,H T并正常OGTT和高胰岛素血症 (H IS) (n=88,6 2 .8% ) ;3组 ,HT并糖耐量低下和 HIS(n=2 5 ,17.9% )。另外 5 2例 H T并 型糖尿病为 4组。发现肾病和脑血管病 (出血、梗塞和短暂性脑缺血发作 )从 1组至 4组逐渐增加 ,3组和 4组之间无显著性差异。4组间左室重量指数无差异 ,心脏收缩和舒张功能减退 ,频发室早和房早的发生率从 1组至 4组递增。说明 H T并 H IS病人的靶器官损害发生率是介于 H T不并 HIS和 H T并 型糖尿病之间的中间类型。依器官损害观点 ,高血压并 H IS可能是单纯高血压 -高血压并 型糖尿病的一种过渡症侯群     

Metabolic Clearance of Norepinephrine in Normotensive and Borderline Hypertensive Subjects

Metabolic clearance of norepinephine (CmNE) has been calculated in 10 normotensive subjects (NT) and 10 borderline hypertensive subjects (HT) at two different infusion rates of 1-NE. Plasma catecholamines have been determined by radio-enzymatic method from arterial blood samples. In these conditions, CmNE is similar in NT and HT.     

Venous Volume in Offspring of Hypertensive Patients

Abstract Twenty normotensive healthy male offspring of hypertensive patients were compared to 20 adequate controls regarding venous volume, the effect of ouabain on venous volume and signs of left ventricular hypertrophy. Among offspring there were slightly increased amplitudes in the orthogonal ECG as compared to controls but the differences were not statistically significant. Using a plethysmographic technique we found a significantly lower venous volume of the forearm in the offspring than in controls. There was, however, no effect of ouabain on the venous volume. The decreased venous distensibility among normotensive offspring might be an early manifestation of essential hypertension.     

Hypotensive Properties of the Protein Kinase Inhibitor,Staurosporine, in Normotensive and Spontaneously Hypertensive Rats

The protein kinase inhibitor, staurosporine, was examined for hemodynamic actions in conscious rats and for its effects on isolated vascular smooth muscle. In conscious normotensive rats, staurosporine, 0.1 to 1.0 mg/kg intravenous, produced a dose-related decrease in blood pressure. Doses of 0.1 and 0.5 mg/kg produced reflex tachycardia, while heart rate decreased following 1.0 mg/kg. Higher doses of staurosporine (5 and 10 mg/kg), although not significantly altering heart rate, caused a precipitous drop in blood pressure and all rats died within 48 hours of treatment. Spontaneously hypertensive rats were significantly more sensitive than normotensive rats to the blood pressure lowering effects of staurosporine. The depressor activity of staurosporine was also observed in cord-stimulated pithed rats indicating that hypotension is a peripherally-rather than centrally-mediated effect of staurosporine. In ring preparations of rat thoracic aorta, staurosporine (3 nM to 0.1 mM) produced a concentration-dependent inhibition of serotonin-induced contraction, consistent with its ability to lower blood pressure by an effect at a peripheral vascular site. These results provide the first documentation of the potent cardiovascular activity of staurosporine in the conscious rat and support the contention that protein kinases, in particular protein kinase C, may be important in the regulation of vascular tone.     

Basal and Postprandial Serum Levels of Gastrin in Normotensive and Hypertensive Adults

Gastrin is a peptide hormone, which acts not only to regulate gastric acid secretion, but also to exert physiological actions such as the regulation of sodium balance. From a case (n = 95)–control (n = 82) study in Fuyang People’s Hospital, Anhui Province, China, we found that the fasting serum gastrin levels are similar in normotensive and hypertensive adults but increased to higher levels in the latter group than in the former group after a mixed meal. We suggest that gastrin is involved in the regulation of blood pressure, possibly via the regulation of sodium and water metabolism and/or renin–angiotensin–aldosterone system. However, the mechanism remains to be determined.     

Blood Pressure and Metabolic Effects of ACTH in Normotensive and Hypertensive Man

ACTH administration (0.5 mg Synacthen Depot I/M 12 hourly for 5 days) significantly increased systolic blood pressure in normotensive subjects (n=6) and mild essential hypertensives (n=6) but not in 2 Addisonian women, indicating that the pressure rise was adrenally dependent. ACTH administration was associated with urinary sodium retention, hypokalaemia, elevation of fasting blood glucose, lymphopaenia and eosinopaenia. Body weight was increased only in the normotensive subjects. Plasma renin concentration fell and renin substrate rose. Inactive renin fell in the hypertensive subjects only. Plasma cortisol, 11-deoxycortisol, corticosterone, deoxycorticosterone, 17α-hydroxyprogesterone and 17-hydroxy, 20-dihydroprogesterone were all increased by ACTH treatment. Plasma aldosterone rose initially in the normotensives but then fell. ACTH administration in man produces metabolic and hormonal changes similar to those produced by ACTH in sheep but the rise in bloodpressure is systolic only in man. The steroid(s) responsible for the blood pressure rise with ACTH in man have not been defined.     

A Pressor Substance in the Cerebrospinal Fluid of Normotensive and Hypertensive Patients

A pressor polypeptide was isolated from the cerebrospinal fluid of normotensive and hypertensive patients. Pharmacologically it behaves like angiotensin I. A very significant correlation (r = 0.83, P < 0.001) was found between the concentration of this polypeptide and the blood pressure of essential hypertensive patients.     

Immediate Hemodynamic Changes Produced by Urapidil in Normotensive and Spontaneously Hypertensive Rats

The immediate effects on regional and systemic hemodynamics of urapidil (1 mg/kg IV), a recently synthesized vasodilator with a possible combined central and peripheral action, were studied in spontaneously hypertensive (SHR) and normotensive (WKY) rats. Maximal decrease in mean arterial pressure was achieved within the first minute after injection (154 ± 4 vs 113 ± 6 mm Hg in SHR and 111 ± 4 vs 82 ± 4 mm Hg in WKY, p < 0.01). This effect was accompanied by a transient (10 min) significant increase in heart rate in both strains. There was a significant fall in total peripheral resistance (0.43 ± 0.02 vs 0.30 ± 0.02 U/kg in WKY and 0.62 ± 0.03 vs 0.43 ± 0.03 U/kg in SHR, p < 0.01) and rise in cardiac index 15 min after drug injection (371 ± 9 vs 425 ± 12 m1/min/kg in WKY and 395 ± 8 vs 432 ± 12 ml/min/kg in SHR, p < 0.01). Organ vascular resistance decreased significantly in all the organs of WKY and most of the organs of SHR rats. However, a significant increase in blood flow was observed only in skeletal muscle. The data indicate that urapidil is a potent hypotensive agent. The pressure fall is mediated through a decreased total peripheral resistance that is distributed through all circulations. The increased cardiac output and heart rate are most likely reflexly induced.