Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In isolated blood vessels, acetylcholine releases endothelium-derived relaxing factor (EDRF). In vivo, the vasodilator action of acetylcholine may be mediated by EDRF, but prostacyclin or prejunctional inhibition of adrenergic neurotransmission may also be involved. Therefore, we investigated whether acetylcholine releases EDRF in humans in vivo and, if so, whether the response altered in essential hypertension. Acetylcholine was infused into the brachial artery, and forearm blood flow measured by venous occlusion plethysmography. In control subjects, acetylcholine (0.02-16 micrograms/min/100 ml tissue) increased flow from 2.4 +/- 5.0 to 20.6 +/- 5.2 ml/min/100 ml tissue (n = 14; p less than 0.05) and decreased forearm vascular resistance from 42.0 +/- 4.1 to 6.0 +/- 1.4 units (p less than 0.03), a response comparable to that of sodium nitroprusside (0.6 micrograms/min ml tissue). Acetylsalicylic acid (500 mg i.v.) given to block vascular prostacyclin production did not alter the response (n = 14). alpha-Adrenoceptor blockade by phentolamine (12 micrograms/min/100 ml tissue) did not prevent the increase in flow evoked by acetylcholine. In hypertensive patients, the decrease in forearm vascular resistance induced by acetylcholine but not evoked by sodium nitroprusside was reduced as compared with controls (14.5 +/- 3.1 and 6.1 +/- 1.6 units, respectively; n = 8; p less than 0.05). Thus, the vascular effects of acetylcholine in the human forearm circulation are independent of prostaglandins and adrenergic neurotransmission and therefore are most likely to be mediated by EDRF; the acetylcholine-induced release of EDRF is blunted in patients with essential hypertension.
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PMID:Indirect evidence for release of endothelium-derived relaxing factor in human forearm circulation in vivo. Blunted response in essential hypertension. 234 73

A group of 89 apparently healthy subjects and 175 patients with essential hypertension (EH) and systolic (atherosclerotic) hypertension aged 25 to 74 years were surveyed. The healthy subjects were found to have changes in prostaglandin (PG) synthesis and metabolism: a reduction in blood plasma concentration of PGE2 and its urinary excretion, a rise in plasma PGF2 level, and, generally, increase in the pressor and decrease in depressor potentials of the PG system. In the EH patients, changes in the PG synthesis and metabolism were unidirectional and had quantitative variations. The differences in the PG levels of healthy and EH-afflicted individuals were found to become less marked with age. The patients with systolic hypertension exhibited higher plasma prostacyclin concentrations as compared to the age-matching control, which is evidence of a lower pressor potential of the PG system than that of the EH patients. The nature and magnitude of changes in the PG system play a certain role in blood pressure formation and in development of the hemodynamic variant of arterial hypertension.
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PMID:[Age-related characteristics of the prostaglandin system in healthy subjects and in patients with arterial hypertension: hypertonic disease and systolic (atherosclerotic) hypertension]. 235 36

Fourteen patients with mild to moderate essential hypertension were randomized, after a baseline placebo period of 4 weeks, to receive the angiotensin converting enzyme (ACE) inhibitor quinapril or a placebo. During a 12 week, double-blind phase, the dosage of quinapril was increased from 10 to 40 mg twice daily being doubled every 4 weeks. At the end of the baseline period and of each month of the double-blind phase, 12 h overnight urine collections were made and morning blood samples were taken about 12 h after the last dose of medication. During the double-blind phase, blood pressure in the quinapril group (n = 7) decreased from 159 +/- 3/105 +/- 1 to 141 +/- 6/94 +/- 2 mm Hg (mean +/- SEM). Serum ACE activity and plasma angiotensin II concentration were reduced to 4 +/- 1% and 14 +/- 1% of the pretreatment values, respectively. Neither the plasma concentrations nor the urinary excretions of prostaglandin E2, 6-keto-prostaglandin F1 alpha (a prostacyclin metabolite), or thromboxane B2 (a metabolite of thromboxane A2) were affected by quinapril. In the placebo group, blood pressure tended to decline but the biochemical variables remained essentially unchanged. These results indicate that prostanoids are not involved in the antihypertensive action of quinapril, the principal effect of which seems to be inhibition of the renin-angiotensin system.
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PMID:Effects of the converting enzyme inhibitor quinapril (CI-906) on blood pressure, renin-angiotensin system, and prostanoids in essential hypertension. 245 40

To evaluate the acute hemodynamic, both systemic and renal, and humoral effect of three increasing doses of Iloprost, a prostacyclin analogue, eight uncomplicated untreated hospitalized patients with mild to moderate essential hypertension, while on a constant sodium and potassium intake, received, after oral hydration, three doses of Iloprost (1,2 or 4 ng/kg/body weight for 45 min) in a single-blind randomized sequence. Each dose was preceded by placebo (saline infusion for 45 min) with a 48 h interval between each study. Iloprost significantly (P less than .05) reduced blood pressure, and increased heart rate, filtered sodium, urinary sodium excretion, fractional sodium excretion, noradrenaline, adrenaline, and plasma renin activity (PRA). The blood pressure lowering effect as well as the heart rate, renal plasma flow and noradrenaline increases were significantly greater on the 4 ng dose. Glomerular filtration rate and adrenaline showed a dose-dependent increase; urinary sodium excretion and fractional sodium excretion were similarly increased by the three doses. No correlation was found between urinary sodium excretion and either glomerular filtration rate or renal plasma flow. The data obtained indicate that Iloprost causes reduction of blood pressure with a reflex activation in the sympathetic nervous system and stimulation of renin secretion, renal vasodilation mainly at the level of the afferent arteriole, and natriuresis. This latter effect is probably due to a direct inhibition of tubular reabsorption, which, at variance with the other effects, is dose-independent.
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PMID:Acute hemodynamic (systemic and renal) and humoral effects of three increasing doses of iloprost in essential hypertensives. 248 Jan 47

To clarify the role of prostacyclin (PG) I2 and thromboxane (TX) A2 in the regulation of blood pressure from the standpoint of acquired factors and hereditary factors, the following experiments were carried out. [1] A low salt diet (2 g/day) was given for 7 days, followed by a high salt diet (23 g/day) for 7 days to 34 patients with essential hypertension. The percent change in 6-keto-PGF1 alpha by salt loading was directly proportional to that in mean blood pressure, but there was no significant relationship between the percent change in TXB2 and that in mean blood pressure. [2] The aorta was removed from 5-week-old and 20- to 25-week-old spontaneously hypertensive rats (SHRs) and age-matched Wistar Kyoto (WKY) rats. Each aorta was incubated in Tris buffer with and without arachidonic acid (AA). There was no significant difference in 6-keto-PGF1 alpha production between SHRs and WKY rats at the age of 5 weeks, but the aorta obtained from 20- to 25-week-old SHRs synthesized about 1.5 times as much 6-keto-PGF1 alpha as did that from age-matched WKY rats with and without AA. The aorta from 5-week-old SHRs synthesized more TXB2 than did that from age-matched WKY rats with and without AA, but there was no significant difference in TXB2 production between SHRs and WKY rats at the age of 20-25 weeks. These data suggest that the plasma PGI2 may have increased as a homeostatic reaction to the elevation of blood pressure induced by salt loading.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of prostaglandin I2 and thromboxane A2 in the regulation of blood pressure. 250 11

Understanding the sequence of events responsible for pressure-related natriuresis and their pathophysiologic alterations may be useful in distinguishing various types of essential hypertension of renal origin. The perturbation of a distal step in the sequence is likely to be reflected in a simple physiologic defect. For instance, pathophysiologic alterations in the medullary production of prostaglandin E2 might directly influence natriuresis and diuresis because of its modulatory effect on tubular reabsorption of sodium and water. Perturbation of more proximal steps in the sequence could influence all the distal events as well. For instance, prostaglandin I2 and endothelium-derived relaxing factor may be produced by the preglomerular vasculature in response to alterations in renal perfusion pressure and may modulate the release of renin from the juxtaglomerular cells. Thus, variations in the production of prostaglandin I2 or endothelium-derived relaxing factor may be reflected by various renal vascular, tubular, and systemic homeostatic events related to the renin-angiotensin system.
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PMID:Alterations in blood pressure by derangement of the mechanisms that regulate sodium excretion. 251 60

Cicletanine chlorhydrate (C), a furopyridine derivative, is a new antihypertensive drug that acts mainly by enhancing endogenous prostacyclin release. It has been shown to induce a significant, progressive reduction in systolic and diastolic blood pressure in patients over 60 years of age at a daily dose of 150 mg in a placebo-controlled efficacy trial. As concurrent studies in adult hypertensive patients demonstrated an antihypertensive effect at even lower doses, we further compared the antihypertensive efficacy and tolerance of 50 mg vs 100 mg daily dose of C in elderly hypertensive patients in order to determine the lowest active posology. A prospective, double-blind randomized trial included 72 patients (56 female, 16 male) aged 65 years or more (mean age +/- 1 SD: 80.3 +/- 5.9 years, range 65-90) with moderate, essential hypertension, and normal-for-age renal function whose diastolic BP was greater than 95 mmHg and/or systolic BP was greater than 160 mmHg after 15 days of a single-blind placebo period. They were randomly allocated to either 50 mg (group I, 36 patients) or 100 mg (group II, 36 patients) C given in a single morning dose for 3 months with monthly surveillance. Of them, 60 achieved satisfactory BP control with C as monotherapy and completed full follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Comparative study of 2 dosages of a new antihypertensive agent, cicletanine, in elderly subjects]. 251 51

The main vasodepressor hormone systems are the kallikrein-kinin systems and the vascular prostacyclin. Kallikreins release kinins which are the biological active compounds of the kallikrein-kinin systems. Kinins are one of the most potent vasodilators reducing systemic blood pressure by diminution of vascular resistance. The reduction in blood pressure is strongly dose related. Prostacyclin develops similar effects on blood pressure as kinins. There is a close relationship between kinins and prostacyclin since kinins stimulate prostacyclin synthesis very effectively. In arterial hypertension there is a lack in kallikrein-kinin and prostacyclin activity. This could also be shown under experimental conditions in spontaneously hypertensive and in Dahl salt-sensitive rats. In clinical studies these experimental results were confirmed in primary hypertension. The blood pressure response to exogenous vasodepressor hormones is increased in hypertensives suffering from reduced endogenous vasodilator activity. In the knowledge of reduced vasodilator activities in primary hypertension the stimulation of kinins by prostacyclin will be of major interest in the management of primary hypertension. In the last years some drugs have been investigated with regard to their kinin prostacyclin stimulating effect, but only angiotensin converting enzyme inhibitors, linolenic acid and cicletanin seemed to induce therapeutic prostacyclin stimulation. However, it remains unclear whether these drugs develop their blood pressure lowering effect by stimulation of the discussed vasodilators or by some other effect.
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PMID:Role of kinins and prostacyclin in blood pressure regulation. 251 56

The purpose of this study was to evaluate the level of renal synthesis of vasodilator and natriuretic prostaglandins I2 and E2 in patients with essential hypertension and to test the effect of cicletanine, a new antihypertensive drug, on the renal synthesis of these prostanoids in hypertensive patients. The first part of the study was carried out in 12 healthy normotensive subjects and in 25 patients of both sexes with essential hypertension. The effect of cicletanine administered in dose of 150 mg was assessed in 10 healthy volunteers and 12 hypertensive patients. The urinary levels of prostaglandins 6-keto-PGF1 alpha (a metabolite of prostacyclin PGI2) and PGE2 were measured (HPLC) by radioimmunoassay after extraction and chromatographic separation. In normal subjects the urinary excretion rate of 6-keto-PGF1 alpha was 134 +/- 26 pg/min and that of PGE2 was 180 +/- 25 pg/min. The corresponding values were significantly lower in hypertensive patients. This defect of PGI2 and PGE2 renal synthesis was found in 64 p. 100 and 72 p. 100 respectively of patients with hypertension. Cicletanine increased the urinary excretion of 6-keto-PGF1 alpha by 45 p. 100 and that of PGE2 by 59 p. 100 in hypertensive patients. It also brought to normal limits the secretion of these prostanoids in these subjects. At the dose of 150 mg the drug stimulated natriuresis significantly and increased glomerular filtration in patients with essential hypertension. This renal effect of cicletanine was acutely reduced by the presence of indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Reduction of kidney prostaglandin synthesis in patients with essential hypertension. Stimulating effect of cicletanine]. 251 74

The effects of sodium intake on blood pressure and platelet function were evaluated in 19 subjects with essential hypertension (10 men and 9 women; mean age 49.7 years). The study was conducted under 3 conditions: (1) normal sodium diet (12 g/day of salt was used in cooking), (2) after 5 days of mild sodium restriction diet (6 g/day of salt was used in cooking) and (3) after moderate sodium restriction (no salt was used in cooking). Blood pressure was significantly reduced following sodium restriction without any change in heart rate. The ratio of the plasma level of beta-thromboglobulin to platelet factor IV, regarded as the most reliable index for platelet activation in vivo, increased significantly after mild sodium restriction; this change was maintained after moderate sodium restriction. Plasma thromboxane B2, a stable metabolite of thromboxane A2, increased significantly after sodium restriction; the level of 6-ketoprostaglandin F1 alpha, a stable metabolite of prostacyclin, was unaffected. These results indicate that dietary sodium restriction induces both a reduction of blood pressure and an activation of platelet function in vivo. Thus, one must consider both antihypertensive effects and effects on platelet function as factors in adjusting the dietary sodium intake in the course of antihypertensive therapy.
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PMID:Effect of sodium restriction on platelet function in patients with essential hypertension. 252 81


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