Plasma endothelin is increased in early essential hypertension

Local vascular generation of endothelin-1 (ET-1) may contribute to elevated peripheral resistance in hypertension. We tested the hypothesis that immunoreactive ET production in the forearm circulation is increased in early essential hypertensive subjects. Ten young, previously untreated male patients with mild essential hypertension and no signs of target organ damage were compared with matched normotensive subjects in an outpatient setting. Arterial and venous samples were obtained from indwelling catheters in the brachial artery and the medial cubital vein, respectively. Samples were collected at baseline and after induction of endothelium-dependent (acetylcholine) vasodilation. Immunoreactive ET (ET) was measured after column extraction by a sensitive radioimmunoassay employing a C-terminal ET-1 antibody with negligible cross-reaction to big-ET. Individual recovery rates were determined for each sample.Basal ET was significantly higher in hypertensive than in normotensive subjects, both in venous and arterial samples (P < .01). This difference was also present after correction for recovery (P < .01). There was no significant difference between venous and arterial ET concentrations. Local vasodilation did not change arterial or venous ET levels. In conclusion, plasma ET is increased in young, untreated, essential hypertensive subjects with no signs of target organ damage. The increased circulating immunoreactive ET may point to a role for the peptide early in the development of high blood pressure.     

高血压病患者血浆内皮素的改变及其临床意义

目的　探讨内皮素 ( ET)与高血压的发病关系及其临床意义。方法　采用放射免疫法检测高血压病 ( EH )患者血浆 ET水平 ,同时与健康人作对照分析。结果　 ( 1) EH患者血浆 ET浓度为 ( 59.71± 2 2 .77) ng/L ,明显高于正常组 ( 37.36± 13.2 7) ng/L ( P <0 .0 1) ;经治疗后 EH患者的 ET浓度明显降低 ,但仍高于正常组 ( P <0 .0 1)。 ( 2 ) 1级高血压病患者血浆 ET浓度最低 ,2级居中 ,3级最高 ,各级之间比较 ,差异有显著性 ( P<0 .0 1)。 ( 3)高血压并发心力衰竭组血浆 ET浓度明显高于无心力衰竭组 ( P<0 .0 1)。结论　 ET参与高血压的发生和发展 ,并与病情有关 ;检测血浆 ET浓度可作为判断 EH患者病情的指标     

Plasma immunoreactive endothelin-1 in experimental malignant hypertension.

We measured plasma concentrations of immunoreactive endothelin-1 (irET-1) in the prehypertensive and hypertensive phases in spontaneously hypertensive rats (SHR) and in malignant hypertension caused by deoxycorticosterone acetate (DOCA)-salt administration in SHR. We also measured concentrations of this peptide in another model of malignant hypertension, the two-kidney, one clip (2K1C) renovascular hypertensive rats chronically given caffeine. Plasma irET-1 concentrations in young (6-week-old) and mature (18-week-old) SHR did not differ from those of age-matched Wistar-Kyoto (WKY) rats. Four weeks of treatment with DOCA-salt increased blood pressure, blood urea nitrogen, serum creatinine, and plasma irET-1 in SHR but not in WKY rats. Eight weeks of DOCA-salt treatment further increased these values in SHR. Plasma irET-1 concentrations were not increased in the 2K1C rats. Six weeks of caffeine administration increased blood pressure, blood urea nitrogen, serum creatinine, plasma renin activity, and plasma irET-1 in the 2K1C rats but not in the sham-operated rats. High-performance liquid chromatographic profiles of plasma extracts pooled from these rats with malignant hypertension showed that a major component of irET-1 eluted in the position of synthetic ET-1 (1-21). Furthermore, acute hypertension induced by angiotensin II or phenylephrine did not affect the plasma irET-1 concentration in rats. The results suggested that the plasma ET-1 concentration is increased in rat models of malignant hypertension and that the high blood pressure itself is not the main factor involved in the increase of plasma ET-1.     

Plasma endothelin levels in hypertension and chronic renal failure

Endothelin-1 is a novel endothelium-derived vasoconstrictive peptide. Using a highly specific and sensitive radioimmunoassay for endothelin-1, plasma levels of immunoreactive endothelin-1 were measured in 32 research subjects with normal renal function (21 normal subjects and 11 patients with essential hypertension), 24 patients with nondialyzed chronic renal failure, and 51 patients undergoing maintenance hemodialysis. Although there was no significant difference in plasma immunoreactive endothelin-1 levels among the three groups, patients with essential hypertension had significantly higher plasma endothelin-1 levels than normal subjects (2.29 +/- 1.09 vs. 1.41 +/- 0.50 pg/ml, p less than 0.025). When nondialyzed and hemodialyzed patients were divided into hypertensive and normotensive groups, the nondialyzed hypertensive group (n = 17) had higher plasma endothelin-1 levels than the comparable normotensive group (n = 7) (3.08 +/- 3.43 vs. 0.73 +/- 0.34 pg/ml, p less than 0.05), and the hemodialyzed hypertensive group (n = 18) had higher plasma endothelin-1 levels than the comparable normotensive group (n = 33) (2.66 +/- 1.92 vs. 1.35 +/- 0.73 pg/ml, p less than 0.005). Plasma atrial natriuretic factor, arginine vasopressin, renin activity, and aldosterone concentration did not show significant differences between hypertensive and normotensive individuals or a correlation with plasma endothelin-1 levels. These data suggest that circulating endothelin-1 may be partly involved in the development or maintenance of hypertension in humans.     

Participation of renal and circulating endothelin in salt-sensitive essential hypertension

Salt sensitivity of blood pressure is a cardiovascular risk factor, independent of and in addition to hypertension. In essential hypertension, a conglomerate of clinical and biochemical characteristics defines a salt-sensitive phenotype. Despite extensive research on multiple natriuretic and antinatriuretic systems, there is no definitive answer yet about the major causes of salt-sensitivity, probably reflecting the complexity of salt-balance regulation. The endothelins, ubiquitous peptides first described as potent vasoconstrictors, also have vasodilator, natriuretic and antinatriuretic actions, depending on their site of generation and binding to different receptors. We review the available data on endothelin in salt-sensitive essential hypertension and conclude that abnormalities of renal endothelin may play a primary role. More importantly, the salt-sensitive patient may have blood pressure-dependency on endothelin in all states of salt balance, thus predicting that endothelin receptor blockers will have a major therapeutic role in salt-sensitive essential hypertension.     

Plasma norepinephrine and dihydroxyphenylglycol in essential hypertension

The aim of the present study was to examine whether essential hypertension is associated with altered plasma concentrations of dihydroxyphenylglycol, the principal presynaptic metabolite of norepinephrine. Forearm venous plasma dihydroxyphenylglycol and norepinephrine were determined at rest and during graded orthostasis in 47 normotensive control subjects and 58 outpatients with essential hypertension. There was no group difference in age. At supine rest as well as during sitting and standing, hypertensive subjects had plasma norepinephrine concentrations similar to those in normotensive control subjects, but plasma dihydroxyphenylglycol concentrations were higher than those in normotensive control subjects. Both groups showed a linear relation between plasma dihydroxyphenylglycol (ordinate) and plasma norepinephrine (abscissa). The resulting regression line was steeper (p less than 0.02) and its ordinate intercept higher (p less than 0.01) in hypertensive than in control subjects. Eleven normotensive and 14 hypertensive subjects were also tested 3 hours after desipramine (1.5 mg/kg orally) was administered to inhibit neuronal norepinephrine reuptake. The drug did not alter plasma norepinephrine, but did reduce plasma dihydroxyphenylglycol and did abolish plasma dihydroxyphenylglycol responses to upright posture in both groups of subjects. The mean plasma dihydroxyphenylglycol concentration observed in the presence of desipramine again was higher in the hypertensive than in the control group (p less than 0.01) and closely agreed, in both groups, with the dihydroxyphenylglycol concentration given by the ordinate intercept of the dihydroxyphenylglycol versus norepinephrine regression line in the absence of desipramine.(ABSTRACT TRUNCATED AT 250 WORDS)     

原发性高血压患者血浆儿茶酚抑素水平及作用

目的探讨原发性高血压患者血浆儿茶酚抑素(CST)水平的变化及其与高血压左心室肥厚的关系。方法选择原发性高血压患者136例(高血压组),健康体检者31例(对照组)。高血压组又分为左心室肥厚27例和非左心室肥厚109例。采用酶联免疫吸附法测定血浆CST水平,高效液相色谱分析法测定血浆去甲肾上腺素(NE)水平。结果与对照组比较,高血压组患者血浆CST及NE水平明显升高,血浆CST/NE比值明显降低(P<0.01)。高血压组左心室肥厚患者血浆NE水平较非左心室肥厚患者明显升高(P<0.01);CST/NE比值明显降低(P<0.01)。结论原发性高血压患者血浆CST水平明显升高,但CST/NE在高血压及高血压左心室肥厚患者中均明显降低,CST可能参与了高血压及左心室肥厚的发生。     

原发性高血压患者血浆脂肪酸的研究

目的:探讨原发性高血压患者血浆脂肪酸组成及含量情况。方法:(1)试验分2组,正常对照组选取正常健康者60例。高血压组选取单纯原发性高血压患者56例,采用Morrison法提取血浆脂肪酸,以气相色谱法检测三氟化硼甲脂化的脂肪酸,计算出各组分所占重量百分比。结果:血浆脂肪酸测定结果高血压组与正常对照组比较差异有统计学意义(P<0.05)(1):高血压组血浆总饱和脂肪酸(SFA)增高,其中增高明显的SFA为豆蔻酸、棕榈酸和硬脂酸。(2)单不饱和脂肪酸(MUFA):高血压组的反式油酸明显增高,油酸则较正常对照组明显减少。(3)多不饱和脂肪酸(PUFA):①总PUFA在高血压组明显减低;②n-6PUFA中:高血压组的亚油酸,Υ-亚麻酸,花生四烯酸,二十二碳四烯酸和二十碳三烯酸均较正常对照组低,尤以二十二碳五烯酸降低更明显;③n-3PUFA中:高血压组的α-亚麻酸、二十碳五烯酸及二十二碳六烯酸均明显减少(均P<0.05)。结论:原发性高血压患者血浆中不但豆蔻酸、棕榈酸和硬脂酸及反式油酸较正常人明显增高,而且油酸、亚油酸,α-亚麻酸及二十碳五烯酸及二十二碳六烯酸均较正常人明显降低,Υ-亚麻酸、花生四烯酸、二十碳三烯酸、二十二碳四烯酸和二十二碳五烯酸也较正常人明显缺乏。     

氯沙坦对老年高血压患者血浆内皮素水平的影响

了解老年原发性高血压患者的血浆皮素水平及运用血管紧张素Ⅱ受体拮剂－氯沙坦治疗后血压及ＥＴ的变化。方法采用连续样本自身前后对照法,４４例老年ＥＨ患者按舒张压水平分轻、中、重三组,观察每天用氯沙坦５０ｍｇ前及连续用１２ｗ后血压及血浆ＥＴ的变化,并与２０例非高血压病人在血浆ＥＴ水平方面进行比较。     

Role of endothelin in the increased vascular tone of patients with essential hypertension

We investigated the possible role of endothelin in the increased vasoconstrictor tone of hypertensive patients using antagonists of endothelin receptors. Forearm blood flow (FBF) responses (strain-gauge plethysmography) to intraarterial infusion of blockers of endothelin-A (ETA) (BQ-123) and endothelin-B (ETB) (BQ-788) receptors, separately and in combination, were measured in hypertensive patients and normotensive control subjects. In healthy subjects, BQ-123 alone or in combination with BQ-788 did not significantly modify FBF (P=0.78 and P=0.63, respectively). In hypertensive patients, in contrast, BQ-123 increased FBF by 33+/-7% (P<0.001 versus baseline), and the combination of BQ-123 and BQ-788 resulted in a greater vasodilator response (63+/-12%; P=0.006 versus BQ-123 alone in the same subjects). BQ-788 produced a divergent vasoactive effect in the two groups, with a decrease of FBF (17+/-5%; P=0.004 versus baseline) in control subjects and transient vasodilation (15+/-7% after 20 minutes) in hypertensive patients (P<0.001, hypertensives versus controls). The vasoconstrictor response to endothelin-1 was slightly higher (P=0.04) in hypertensive patients (46+/-4%) than in control subjects (32+/-4%). Our data indicate that patients with essential hypertension have increased vascular endothelin activity, which may be of pathophysiological relevance to their increased vascular tone. In these patients, nonselective ETA and ETB blockade seems to produce a greater vasodilator effect than selective ETA blockade.     

Interactions between sympathetic nervous system and endogenous endothelin in patients with essential hypertension

Experimental evidence indicates that endothelin 1 stimulates the sympathetic nervous system by activation of the subtype A receptor. The aim of the present study was to assess whether this mechanism is active in humans and to investigate its potential role in the pathogenesis of essential hypertension. In 15 hypertensive patients and 12 normotensive subjects, blood pressure, heart rate, and muscle sympathetic nerve activity were evaluated during intravenous 20-minute infusion of BQ123 (0.1 mg/kg per hour), an endothelin A receptor antagonist, and sodium nitroprusside (SNP; 0.4 μg/kg per minute). In hypertensive patients, blood pressure was reduced similarly by BQ123 and SNP. In contrast, the increase in muscle sympathetic nerve activity induced by BQ123 (from 52.0 ± 4.9 to 56.8 ± 5.5 bursts per 100 heartbeats; P<0.05 versus baseline) was significantly lower (P<0.05) than that induced by SNP (from 50.6 ± 4.9 to 61.1 ± 5.1 bursts per 100 heartbeats; P<0.05 versus baseline). In normotensive subjects, SNP reduced blood pressure and increased muscle sympathetic activity, whereas BQ123 was ineffective. Thus, in a subgroup (n = 9) of normotensive subjects, we administered BQ123 at a higher dose (0.2 mg/kg per hour), representing an equidepressor dose of SNP, inducing a blunted increase in sympathetic activity (from 44.1 ± 2.4 to 50.1 ± 6.4 bursts per 100 heartbeats; P<0.05 versus baseline). Finally, administration of a different vasodilator (papaverine, 0.5 mg/kg per hour) exerted results superimposable to SNP. Endogenous endothelin 1 appears to have a sympathoexcitatory effect both in normotensive and hypertensive subjects through endothelin A receptors, contributing to basal sympathetic vasomotor tone. Moreover, essential hypertension shows an increased susceptibility to the sympathoexcitatory effect of endogenous endothelin 1.     

老年高血压病病人血浆内皮素与左室收缩期峰值室壁应力及周围总阻力的关系

检测３３例老年高血压病（ＥＳＨ）病人血浆内皮素（ＥＴ）及血液动力学指标的变化，结果表明，ＥＴ及左室收缩期峰值室壁应力（ＰＳＳ）、周围总阻力（ＴＰＲ）均明显高于健康对照组，且ＥＴ与ＰＳＳ、ＴＰＲ间均存在着显著正相关（Ｐ＜００１）。提示ＥＴ在促进ＰＳＳ、ＴＰＲ增高方面起很重要的作用。     

Plasma levels of cyclic nucleotides in patients with essential hypertension

We studied plasma levels of cyclic nucleotides and their responses to submaximal exercise as an endogenous adrenergic stimulation in normal subjects, untreated and treated patients with essential hypertension to assess the roles of various hormones and the autonomic nervous system in essential hypertension. Plasma c-AMP level was significantly higher in untreated, diuretic-treated patients and those treated with propranolol than in normal subjects, but plasma c-GMP level was comparable in normal subjects and untreated patients. Plasma c-AMP decreased significantly, whereas plasma c-GMP increase significantly, after chronic propranolol therapy. Plasma c-AMP increased significantly after submaximal exercise in normal subjects, untreated patients and those treated with propranolol, but plasma c-GMP increased significantly only in normal subjects. The increase in plasma c-AMP was significantly higher in untreated patients than in normal subjects and patients treated with propranolol. Moreover, the percent increase in plasma c-AMP was significantly higher in untreated patients than in those treated with propranolol. Therefore, it is suggested that the sympathetic nervous system may be hyperactive, and that a hyperreactivity of the beta-adrenergic receptors may play an important role in essential hypertension.     

Plasma digitalislike activity in essential hypertension or end-stage renal disease

Plasma extracts from 119 subjects showed a digitalislike activity, as evidenced by the ability of these extracts to inhibit ouabain binding to the Na+-K+ pump. High levels of the digitalislike compound were found in 18 of 54 untreated hypertensive subjects, 7 of 21 normotensive subjects with a family history of hypertension, and 10 of 14 patients with end-stage renal failure. Dialysis significantly reduced the activity of this compound. These results suggest 1) that endogenous digitalislike factor is not directly linked to hypertension but rather is related to sodium balance and 2) that it neither originates nor is activated by renal tissue, as it was present in four of six anephric patients.     

高血压病患者血浆降钙素基因相关肽和内皮素浓度的变化

目的 :探讨血浆降钙素基因相关肽 （CGRP）和内皮素 （ET）与高血压病之间关系。方法 :放射免疫方法检测 2 5例正常人和 36例高血压病患者降压治疗前后血浆 CGRP和 ET浓度 ,同时测量高血压病患者血压。结果 :1高血压病患者血浆 CGRP浓度低于正常人 ,与平均动脉压呈负相关 ;ET浓度高于正常人 ,与平均动脉压呈正相关。2有效降压治疗后 ,高血压病患者血浆 CGRP浓度回升 ,ET浓度下降 ,CGRP/ ET比值明显升高。结论 :血浆 CGRP和ET浓度失衡可能是高血压病发生的重要原因之一 ;有效降血压可能与 CGRP和 ET的变化有关。