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)

Vasodilator substances released in the blood vessel wall, such as the endothelium-derived relaxing factor (EDRF) and prostacyclin (PGI2), may participate in the regulation of arterial blood pressure. However, their role in the pathogenesis of human essential hypertension to date remains unclear. For some of these factors affecting vascular smooth muscle cells, blood platelets represent a second target tissue. Thus, EDRF and PGI2 inactivate platelets by stimulation of cyclic guanosine-5'-monophosphate (cGMP) and cyclic adenosine-5'-monophosphate (cAMP) synthesis, respectively. In the present study, platelet cAMP (n = 68) and cGMP (n = 60) were determined in a control group of healthy subjects (C) and in 12 patients with untreated essential hypertension (EH). In the control group, platelet cAMP and cGMP content averaged 13.52 +/- 0.38 and 1.48 +/- 0.06 pmol/10(9) platelets and no dependence of either variable on sex or age could be established. Furthermore, cGMP levels were similar in EH as compared to the control group (1.38 +/- 0.11 pmol/10(9) platelets). However, intracellular concentrations of cAMP were significantly lower in EH as compared to C (11.22 +/- 1.37 pmol/10(9) platelets; P < .01). In addition, we investigated the stimulatory effect on cAMP of the stable PGI2 analog iloprost (10(-9), 5 x 10(-9), 10(-8), 5 x 10(-8) mol/L) in the platelets of 12 control subjects (C12) and EH.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Platelet cAMP and cGMP in essential hypertension. 128 Sep 52

Vascular formation of prostacyclin is increased by propranolol in patients with essential hypertension. However, the possible effect of beta-adrenoceptor blocking drugs in healthy subjects is, however, not known. We studied this issue by analysis of the urinary excretion of the prostacyclin metabolite, 2,3-dinor-6-keto-prostaglandin F1a during intake of a beta 1-selective (metoprolol) or a non-selective (propranolol) beta-adrenoceptor antagonist. After 14 days of metoprolol treatment (100 mg d-1) the urinary excretion of PGI-M did not differ from control (253 +/- 77 vs. 220 +/- 33 pg mg-1 creatinine, respectively). Five days of randomized cross-over treatment with propranolol (80 mg day-1) or placebo did not affect urinary PGI-M significantly either (177 +/- 11 vs. 202 +/- 11 pg mg-1 creatinine, respectively). Furthermore, a daily increasing dose of propranolol (80-480 mg) progressively lowered resting blood pressure and heart rate, but failed to influence urinary excretion of PGI-M. The data demonstrate that metoprolol and propranolol do not affect basal cardiovascular formation of prostacyclin in healthy subjects. Thus, the biosynthesis of prostacyclin does not appear to be regulated by beta-adrenoceptor activity under normal conditions.
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PMID:Formation of prostacyclin during administration of beta 1-selective and non-selective beta-adrenergic antagonists in healthy humans. 134 60

To evaluate platelet activation thromboxane A2 (TxA2) and beta-thromboglobulin (beta TG) were used as markers and in addition we studied the biosynthesis of prostacyclin. Synthesis of TxA2 and prostacyclin was assessed by measurement of urinary metabolites. Fifteen untreated hypertensive patients (HT) and 15 age-matched normotensive controls (NT) were investigated at rest, during and after exercise. HT patients were re-examined after 3 months on enalapril. During basal conditions there was no difference in the excretion of Tx-M, PGI-M or beta TG between the groups. During strenuous exercise HT exhibit a significantly higher increase in prostacyclin synthesis (162%) compared to NT (76%). The levels of beta TG increased with 82% in the HT and 24% in the NT group, Tx-M increased with 27% and 23% respectively. Treatment with the ACE-inhibitor enalapril did not significantly alter these findings. These results indicate that there is no evidence of basal platelet activation in early essential hypertension. Strenuous exercise leads to some increase in Tx-M in both groups, with no pronounced differences between the groups. Hypertensive patients exhibit a significantly increased prostacyclin response to exercise which could be due to differences in vessel-wall reactivity. Enalapril seems to exert no effect on platelet activation or on prostacyclin biosynthesis.
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PMID:Platelet activation and prostacyclin release in essential hypertension. 141 May 27

Prostacyclin (PGI2) is known to cause vasorelaxation and inhibit platelet aggregation by receptor-mediated mechanisms. While cyclic (c) AMP is known to act as a second messenger for inhibition of platelet aggregation, vasorelaxation by hyperpolarization has been described only recently and may provide an explanation, in addition to stimulation of cAMP for the PGI2 mechanism of action on blood vessels. When PGI2 is infused into healthy volunteers it reduces blood pressure only at infusion rates that also cause significant side-effects, primarily, nausea, emesis, flushing, diaphoresis, and restlessness. In hypertensive patients blood-pressure responses are complex and are influenced to some extent by renin secretion. PGI2 stimulates renin secretion by a direct effect on the juxtaglomerular apparatus, and it also has an indirect effect by activating the sympathetic nervous system. Thus, it is useless as an antihypertensive agent even apart from its debilitating side-effects. Vascular PGI2 is synthesized endogenously by both the endothelial cells and the muscularis of arteries. While the endothelial cells undoubtedly synthesize large amounts of PGI2, the muscularis comprises a much larger tissue mass so that the overall synthesis is about equally distributed between the endothelial and muscle cells. In patients with pregnancy-induced hypertension and some patients with essential hypertension endogenous synthesis of PGI2 has been evaluated by measuring 2,3-dinor-6-keto-PGF1 alpha and has proved to be greatly reduced. Some drugs (thiazides, propranolol) have been shown to stimulate PGI2 synthesis, and inhibition of cyclooxygenase has been shown to reduce their antihypertensive effects. The effects of low- and high-dose aspirin on prostacyclin and thromboxane synthesis are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Prostacyclin in hypertension]. 149 51

To define the role of the renal eicosanoid system in sustaining renal homeostasis in hypertension, we investigated the alterations in urinary excretions of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), a stable metabolite of vasodepressor prostacyclin, and thromboxane B2 (TXB2), a stable metabolite of vasoconstrictor TXA2, when norepinephrine was continuously infused for 90 min in hypertensive (n = 13) and normotensive subjects (n = 14). There was no difference in plasma norepinephrine concentration after the infusion between the hypertensive and the normotensive subjects. Moreover, the percent changes in renal vascular resistance elicited by norepinephrine in the hypertensives were equal to those of the normotensive subjects. In the normotensive subjects, the norepinephrine infusion significantly increased urinary 6-keto-PGF1 alpha excretion and decreased urinary excretion of TX, both of which are beneficial for sustaining renal function. In fact, the greater the production of renal 6-keto-PGF1 alpha was, the less the reduction of renal blood flow and urinary sodium excretion was. In the hypertensive subjects, however, these normal responses of the renal eicosanoid system, seen in the normotensives, were abolished; urinary 6-keto-PGF1 alpha was unaltered and thromboxane generation was rather increased. Thus, the renal eicosanoid system dysfunctions in hypertensive subjects when the renal circulation is challenged by norepinephrine. These abnormal responses are likely to cause sodium retention and could contribute, in part, to the hypertensive mechanism in patients with essential hypertension.
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PMID:Abnormal response of urinary eicosanoid system to norepinephrine infusion in patients with essential hypertension. 150 57

The effects of prostacyclin infusion (6.7 +/- 2.7 ng/kg/min, 3 to 10 ng/kg/min) on blood pressure, plasma renin activity (PRA), and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were studied in 7 patients with essential hypertension (4 men and 3 women) with a mean age of fifty-eight +/- eleven years (forty-six to seventy-four years). The baseline value of 6-keto-PGF1 alpha for patients with essential hypertension was not lower than in healthy subjects. Blood pressure immediately dropped following prostacyclin infusion. Systolic blood pressure returned to the baseline value after prostacyclin infusion was discontinued. However, diastolic blood pressure and mean arterial blood pressure were still significantly decreased thirty minutes after termination of infusion. Heart rate did not change during prostacyclin infusion but decreased significantly when infusion was terminated. PRA was not significantly affected by prostacyclin infusion. The 6-keto-PGF1 alpha level was about 8 times higher than the baseline value thirty minutes after initiation of prostacyclin infusion and approximately twice as high as the baseline value thirty minutes after termination of infusion. The decrease in mean arterial blood pressure coincided with the increase in 6-keto-PGF1 alpha. There was no correlation between mean arterial blood pressure and PRA, nor between PRA and 6-keto-PGF1 alpha. These results demonstrate that production of prostacyclin is not reduced in patients with essential hypertension, and heart rate and PRA are not changed by prostacyclin infusion, although prostacyclin decreases blood pressure.
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PMID:Effects of prostacyclin infusion on blood pressure and plasma renin activity in patients with essential hypertension. 153 71

Evidence continues to accumulate on the importance of paracrine substances formed in the vascular endothelium in the regulation of the vascular system. Those that relax the underlying smooth muscle include nitric oxide, prostacyclin, and an unidentified hyperpolarizing factor; those causing contraction include angiotensin II, endothelin, oxygen-derived free radicals, prostacyclin H2, and thromboxane A2. Determination of the mechanisms governing the formation and release of these substances in different blood vessels of the same species and in different species as well as the maintenance of the balance between them is important for understanding their role in normal circumstances and in diseases of the blood vessels. In this article, we will summarize the current understanding of the role of endothelium-derived relaxing factors and discuss the possibility that endothelial dysfunction may play a primary as well as a secondary role in the pathogenesis of primary hypertension. As a consequence of this dysfunction, substances formed in the endothelial cells at the sites of the arterial baroreceptors could lead to their resetting, resulting in less inhibition of the vasomotor centers, enhanced neurohumoral activity, and a consequential increase in systemic vascular resistance. This increase could be enhanced by a predominant action of endothelium-derived contracting factors in the resistance vessels. Proliferation of the vascular smooth muscle would follow, because of the mitogenic action of some of these factors and other growth promotors. By these mechanisms, the endothelium may participate in the polygenic dysfunction characteristic of primary hypertension, not only in initiating the increase in arterial blood pressure, but also in sustaining it.
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PMID:Endothelium-derived vasoactive factors: I. Endothelium-dependent relaxation. 193 90

A low dose of dopamine (1 microgram/min/kg) infused for 3 h, which is without systemic hemodynamic effects in normal subjects, increased the renal blood flow and renal production of prostacyclin (PGI2). This action was blocked by metoclopramide as well as by either of two cyclooxygenase (CO) blockers, but effects were not altered by administration of the alpha 1 blocker prazosin. Much of the effect of dopamine (DA) is apparently via the DA1 receptor, since fenoldopam (0.1 microgram/min/kg) reproduced these actions. However, although fenoldopam increased glomerular filtration rate and urinary Na+, CO blockers were without effect. In contrast neither DA or fenoldopam infusions changed either renal blood flow or PGI2 in a group of patients with essential hypertension. Renin secretion was shown to be increased via DA1 receptor activation both in humans and rat renal tissue. The DA2 receptor may also play a role since domperidone can reduce renal blood flow.
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PMID:Effect of dopamine on renal blood flow, prostaglandins, renin and electrolyte excretion in normal and hypertensive humans. 197 38

The anti-hypertensive effect of ketanserin, a new antagonist of 5-HT2-serotonergic receptors, was evaluated in 10 patients with uncomplicated essential hypertension. At the end of 2 weeks of placebo wash-out and following 2 and 4 weeks of treatment with ketanserin (20 mg twice daily), blood pressure and heart rate were measured both in the supine and standing position. In addition, before and at the end of treatment, plasma renin activity (PRA), plasma concentration of aldosterone and the nocturnal urinary excretion of 6-keto-PGF1 alpha and TXB2, the two metabolites that largely reflect the renal synthesis of prostacyclin and thromboxane, respectively, were determined. The study was carried out in a metabolic ward where the intake of sodium was adjusted to 100-120 mmol day-1. Ketanserin significantly reduced blood pressure both in the supine and standing position with no significant change of heart rate. The treatment did not produce any variation of PRA, aldosterone, urinary excretion of 6-keto-PGF1 alpha or TXB2. These results indicate that ketanserin reduces blood pressure without interfering with the renin-angiotensin-aldosterone system or the renal synthesis of prostacyclin and thromboxane.
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PMID:Absence of effects of ketanserin on renal prostacyclin and thromboxane A2 in essential hypertension. 206 89

Prostacyclin and thromboxane A2, products of separate branches of the arachidonic acid cascade, can have opposing effects on kidney function and on the vascular musculature. Prostacyclin acts as a vasodilator while thromboxane A2 has a vasoconstrictor effect and the balance between these two compounds appears to contribute to the homeostatic regulation of normal blood pressure. In the hypertensive state, this balance is disrupted and, at least in animal models of hypertension, there is excessive production of both. The increase in prostacyclin formation may be a reaction to the elevated blood pressure, possibly due to mechanical stimulation of the vascular smooth muscle cells in the blood vessel wall. However, the increase in thromboxane A2 may be more directly involved in the development and maintenance of hypertension. Not only is thromboxane A2 a vasoconstrictor but it can also stimulate the growth and proliferation of vascular smooth muscle cells which may account for the vascular hypertrophy seen in hypertension. Both of these actions would increase total peripheral resistance and contribute to hypertension. Whether prostacyclin and thromboxane A2 are in fact involved as causative agents in essential hypertension must await future research.
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PMID:Prostacyclin, thromboxane A2, and hypertension. 207 14


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