Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cause of preeclampsia, a syndrome unique to human pregnancy, is unknown. There is presently no effective pharmacologic therapy once the symptoms have appeared. Only delivery is curative. Preeclampsia likely has multiple etiologies, each of which activates a common pathway, culminating in diffuse endothelial damage, vasospasm, and hypertension. Current investigation suggests that serotonin has a pivotal role in the genesis of preeclamptic hypertension. The evidence, as obtained from human and animal study, is reviewed in this article, and areas in need of further study are highlighted. A modified series of Koch's postulates is employed for a framework. Serotonin is the agent but does not directly cause the hypertension. Rather, it is suggested that in a milieu characterized by a reduction in endothelial-derived relaxing factor and prostacyclin, serotonin augments the smooth muscle response to normally occurring concentrations of endogenous vasopressors. It is delivered to the site of action (the microvasculature) by the platelet, whose aggregation is encouraged by dysfunctional endothelium. Either inhibition of the delivery mechanism by a low, daily dose of aspirin, or inhibition of the peripheral serotonin type 2 (5HT2) receptor, effectively controls the hypertension.
 ...
PMID:The role of serotonin in the preeclampsia-eclampsia syndrome. 228 49

The reduction in blood pressure to normotensive levels within 3 hours of unclipping the one-kidney, one clip Goldblatt hypertensive rat has been attributed to the release of potent blood pressure-lowering lipids, one of which is thought to be identical to platelet activating factor. The specific platelet activating factor receptor antagonist WEB 2086 was infused intravenously into hypertensive one-kidney, one clip rats, and the mean arterial blood pressure changes after unclipping were examined. Before infusion, blocking doses of WEB 2086 were confirmed to effectively abolish the fall in blood pressure induced by exogenous platelet activating factor. Serotonin release in response to exogenous platelet activating factor was also inhibited in platelets preincubated with plasma from rats infused with the antagonist. Hypertensive rats were given a bolus blocking dose of WEB 2086 (5 mg/kg i.v.) and the same dose by infusion (5 mg/kg/hr i.v.) before they were unclipped. A control group was given a bolus volume of saline and infused with saline before unclipping. In WEB 2086-treated rats, blood pressure fell from a baseline mean of 181 +/- 13.0 to 125 +/- 23 mm Hg after 4 hours, a fall of 28%. Saline-treated rats fell from a mean of 194 +/- 23 to 127 +/- 25 mm Hg (33%). There was no significant difference in the blood pressure fall between the two groups. Therefore, platelet activating factor is unlikely to be responsible for the restoration of normal blood pressure after unclipping the Goldblatt hypertensive rat. We attribute the fall in blood pressure to other presently unidentified renomedullary lipids.
Hypertension 1990 Jun
PMID:Platelet activating factor and one-kidney, one clip hypertension. 234 25

Serotonin C1- and C2-receptor binding was studied in various segments of the brain in two strains of rats with hereditary arterial hypertension--spontaneously hypertensive (SHR) and hereditary stress-induced hypertensive rats (HSIHR). In the hypothalamus, there was a higher C1-receptor binding in HSIHR than in Wistar rats. SHR showed a higher C2-receptor binding in the cortex and C1-receptor one in the pons than did HSIHR. The changes found are suggestive of both similarities and differences in the serotonin receptor system in the two strains of rats with hereditary arterial hypertension.
 ...
PMID:[Differences in serotonin receptor types I and II binding in the brain regions of rats with 2 types of hereditary arterial hypertension]. 238 Nov 30

The participation of the central serotonergic system in the development of two-kidney, two clip (2K2C) Goldblatt renovascular hypertension in the rat has been examined. Half of the rats were treated with desmethylimipramine intraperitoneally and 5,7-dihydroxytryptamine intracisternally; the other half received only desmethylimipramine and the 5,7-dihydroxytryptamine vehicle. Two days later, a silver clip was placed in both renal arteries in half of the rats of each group. A sham operation was performed in the remaining rats. Blood pressure was recorded during the 5 weeks after treatment. At the end of the experiment, blood and cerebrospinal fluid samples were obtained. The brain was dissected into several areas and kept frozen. Norepinephrine, serotonin, angiotensinogen, and renin-like concentration were evaluated in the brain areas. Plasma renin activity and angiotensinogen concentration in the plasma and cerebrospinal fluid were estimated. In the sham-operated groups, blood pressure was lower in the treated than in the control rats. The curve of blood pressure increase, as well as the final blood pressure, was similar in the treated and control 2K2C rats. Serotonin was significantly depleted by the 5,7-dihydroxytryptamine treatment in all brain areas. Treatment did not induce any changes in central norepinephrine concentration. Plasma renin activity was diminished in the treated sham-operated rats. These data indicate that the central serotonin depletion does not prevent the development of hypertension and confirm the role of the amine in normal blood pressure regulation. On the other hand, the peripheral renin-angiotensin system might participate in the development of high blood pressure in serotonin-depleted animals.
Hypertension 1990 Feb
PMID:Development of renovascular hypertension after central serotonin depletion. 240 59

Serotonin (5-hydroxytryptamine) causes contraction of most large blood vessels and of venules. This is due mainly to direct activation of the smooth muscle or to amplification of the response to other neurohumoral mediators. Vasodilator responses to serotonin are seen mainly at the arteriolar level. They can be due to the release of other endogenous vasodilators, direct relaxation of vascular smooth muscle, inhibition of adrenergic neurotransmission, or release of an endothelium-dependent relaxing factor(s). Aggregating platelets release enough serotonin to evoke both constrictor and dilator responses. Hence the absence of endothelial cells or of adrenergic nerve activity may change the response to platelets from dilatation to constriction. Vasoconstrictor responses to serotonin released from aggregating platelets may play a role in the maintenance of the augmented peripheral resistance in hypertension. Such an involvement of serotonin is suggested by the following observations in humans and animals: the turnover rate of platelets is accelerated; the uptake of serotonin by platelets is reduced; the metabolism of serotonin by the endothelial cells is decreased; the vascular smooth muscles are hyperresponsive to the constrictor effects of serotonin and other serotonergic agonists; the S2-serotonergic antagonist ketanserin, which is devoid of agonistic properties, lowers arterial blood pressure in hypertensive humans. Whether the alpha-adrenergic blocking properties of ketanserin contribute to its antihypertensive properties in humans is still a matter of discussion.
 ...
PMID:Can peripheral serotonergic blockade explain the hypotensive effect of ketanserin? 241 25

This study examined the effects of the serotonergic (5-HT2) antagonist ketanserin in sheep on haemodynamic responses to infused serotonin (5-HT), development of adrenocorticotrophin (ACTH)-induced hypertension, and the effect of ACTH on in vivo pressor responsiveness to 5-HT. Serotonin produced a dose-related increase in mean arterial pressure and heart rate. These increases in mean arterial pressure were attenuated or abolished by ketanserin, but increases in heart rate were enhanced. Ketanserin modified the pressure response to the alpha-adrenergic agonist phenylephrine, and did not further lower mean arterial pressure in sheep pretreated with the alpha-antagonist prazosin. Thus, ketanserin exhibits alpha-adrenergic antagonism in sheep. Ketanserin infusion lowered mean arterial pressure in normal sheep but did not affect the pressor response to ACTH infusion. There was no difference in pressor responsiveness to 5-HT (0.1-30 micrograms/kg) before and after ACTH treatment. Thus, 5-HT raises mean arterial pressure in sheep in a dose-related fashion, but there is no evidence of a role for 5-HT in ACTH-induced hypertension.
 ...
PMID:Serotonergic mechanisms and blood pressure in sheep. 241 29

The similarity between the metabolic pathways of serotonin in platelets and serotoninergic nerve endings has often been emphasized. The turnover of serotonin was therefore investigated in two diseases: hypertension (as central serotoninergic neurones appear to modulate central sympathetic nervous activity) and depression (as a central 5-HT-deficiency and a low 3H-imipramine binding on platelets have been described in patients with endogenous depression). Mean platelet 5-HT level was significantly lower in essential hypertensives than in controls. A reduction in platelet 5-HT level was also observed in depression and was more marked in women than in men. Serotonin level was only weakly related to the severity of the diseases. In some hypertensive patients, administration of ketanserin resulted in a reduction of blood pressure without affecting 5-HT level. In depressive patients, maprotiline and chlorimipramine acted differently on 5-HT level but both improved the clinical symptoms.
 ...
PMID:Platelet serotonin in essential hypertension and in mental depression. 241 30

Ketanserin, a new selective 5-HT2-serotonergic antagonist, was used to: confirm its hypotensive efficacy in acute and long-term treatment, determine its influence on the influence on the metabolism of serotonin (5-HT) and catecholamines, and elucidate their mutual relationship. Ketanserin was given intravenously to 10 patients with hypertensive crisis or resistant hypertension and orally to 15 patients with mild to severe hypertension for 1 year. Blood pressure, heart rate, 24-h urinary excretion of vanilmandelic acid (VMA; the major endproduct of catecholamines) and of 5-hydroxyindoleacetic acid (HIAA; the endproduct of serotonin metabolism), and platelet aggregation were measured. In doses normalizing blood pressure and platelet aggregation, ketanserin administered to hypertensive patients either intravenously in acute treatment or orally in chronic treatment caused: (a) decreased HIAA excretion (more marked in chronic than in acute treatment) and (b) simultaneous decrease in VMA excretion. It is concluded that the decisive sites of ketanserin action are the 5-HT2 receptors of platelets. The compound reduces platelet aggregation and the release of 5-HT, its metabolism, and, hence, the excretion of HIAA. The action of ketanserin on 5-HT2 receptors of vascular smooth muscle participates in the hypotensive effect of the drug but does not explain the decreased excretion of HIAA and VMA.
 ...
PMID:Blood pressure, 5-OH indoleacetic acid, and vanilmandelic acid excretion and blood platelet aggregation in hypertensive patients treated with ketanserin. 241 52

Serotonin is a vasoactive substance that acts on blood vessels and platelets but whose primary action lies in its role as an amplifier for other agents. The aim of this work was to study the effects on blood platelets and erythrocytes of the S2-serotonergic receptor antagonist ketanserin. Twenty-seven patients with untreated hypertension and/or intermittent claudication received a bolus intravenous (i.v.) injection of 10 mg ketanserin followed by 2 mg/h during 3 h i.v. infusion. Platelet function and erythrocyte filterability were studied before and 30 min, 3 h, and 24 h after the bolus injection. The results showed decreases of plasma beta-thromboglobulin and platelet factor 4 levels (p less than 0.001) and platelet aggregation induced by epinephrine plus serotonin (p less than 0.001), whereas ADP-induced aggregation remained unchanged 30 min and 3 h after ketanserin administration. Red cell filterability was decreased (p less than 0.01). There was a tendency toward lower mean arterial blood pressure but heart rate remained unchanged. The dual effect of ketanserin on platelet function and erythrocyte filterability might be of great clinical value in hypertension and peripheral vascular disease in which microcirculatory flow is altered.
 ...
PMID:Effects of ketanserin on platelet function and red cell filterability in hypertension and peripheral vascular disease. 241 53

Serotonin has several effects on vascular smooth muscle. In most vascular beds it causes vasoconstriction, but under the proper conditions it can cause vasodilatation. The constrictor response is a result of activation of specific receptors on the vascular smooth muscle, whereas the vasodilator response is mediated in part by the vascular endothelium. In addition to these direct effects on the vascular wall, serotonin can potentiate contractile responses to several other vasoactive agents (norepinephrine, angiotensin II, histamine, etc.). This indirect sensitizing action of the monoamine is probably mediated by activation of the S2 subclass of serotonergic receptors. These complex actions of serotonin on vascular smooth muscle may be altered in disease states such as hypertension.
 ...
PMID:Direct and sensitizing effects of serotonin agonists and antagonists on vascular smooth muscle. 241 57


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>