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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The past decade has seen important progress in understanding the localization, pharmacology, and function of serotonin (5-HT) receptor subtypes. At least seven subclasses have been shown to exist, and evidence is emerging to suggest further subclassification. Serotonin is involved in numerous physiological processes (e.g. feeding, sleep, pain, sexual behavior, temperature regulation) and pathophysiological ones. Serotonin reuptake blockers have been found effective in the alleviation of depression and attacks of panic, and are at varying stages of clinical evaluation in the treatment of obsessive compulsive disorder, chronic pain, and bulimia nervosa. Selective potent serotonin receptor agonists and antagonists show promise in the treatment of migraine, nausea and vomiting, schizophrenia, anxiety, hypertension, and Raynaud's disease.
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PMID:[New therapeutic possibilities with drugs affecting serotonin receptors]. 150 27

The effect of a high-affinity C1A serotonin receptor agonist flesinoxan on the arterial blood pressure and the heart rate in normotensive Wistar rats, spontaneously hypertensive rats and inherited stress-induced arterial hypertension rats was studied. It was shown that both peripheral and central administration of flesinoxan produces a decrease of blood pressure and heart rate. However, a reduction of heart rate was more pronounced at the drug peripheral administration. The sensitivity to flesinoxan in the hypertensive rats was greater than in the normotensive rats.
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PMID:[The effect of the flesinoxan subtype of serotonin C1a receptor agonist on the arterial pressure in rats]. 178 17

Evidence suggests that unstable angina, non-Q-wave myocardial infarction and Q-wave myocardial infarcts represent a continuum, such that transient reduction in coronary blood flow associated with platelet aggregation and dynamic vasoconstriction at sites of coronary artery stenosis and endothelial injury lead to abrupt development of unstable angina. Factors potentially responsible for the conversion from chronic to acute coronary artery disease include endothelial injury at sites of stenosis. The endothelial injury may be the result of plaque fissuring or ulceration, hemodynamic factors (including systemic arterial hypertension or flow shear stress), infection, smoking, coronary arteriography or balloon angioplasty. Clinical and experimental animal studies suggest that interference with thromboxane and serotonin contributions to platelet aggregation and dynamic coronary artery constriction may prevent chronic coronary artery disease syndromes from converting to acute disease. To protect against this process may require both thromboxane and serotonin receptor antagonists or a combination of thromboxane synthesis inhibitor and receptor antagonist with a serotonin receptor antagonist. Further studies are needed to test this hypothesis.
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PMID:Potential usefulness of combined thromboxane A2 and serotonin receptor blockade for preventing the conversion from chronic to acute coronary artery disease syndromes. 214 68

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.
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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

Ketanserin is a selective (S2) serotonin receptor antagonist currently under investigation as an antihypertensive. It has been suggested that the antihypertensive action of ketanserin might be principally due to alpha-adrenergic receptor antagonism rather than its effect on serotonin receptors. We therefore determined the contribution of alpha-adrenergic blockade to the hypotensive effects of ketanserin in six patients with hypertension and compared that with the alpha-adrenergic blockade produced by prazosin, a known alpha 1-adrenergic antagonist. Each patient received placebo, ketanserin (40 mg every 8 hours), and prazosin (5 mg every 8 hours). Each agent was administered for 4 weeks in random order. Both ketanserin and prazosin lowered blood pressure significantly and to a similar extent. The extent of alpha-adrenergic blockade was determined from the ability to inhibit the hypertensive effect of phenylephrine infusions. The dose of phenylephrine required to raise the blood pressure by 20 mm Hg was significantly higher during both ketanserin (1.41 +/- 0.27 micrograms/kg/min; p less than 0.05) and prazosin (4.99 +/- 0.77 micrograms/kg/min; p less than 0.01) administration compared with placebo (0.85 +/- 0.15 micrograms/kg/min). However, the dose ratio was more than fourfold higher during prazosin treatment (7.38 +/- 1.99; p less than 0.05) than during ketanserin (1.69 +/- 0.21). Thus at equipotent hypotensive doses the extent of alpha-blockade produced by ketanserin was more than fourfold lower than that of prazosin, implying that mechanisms other than alpha-blockade must contribute to the antihypertensive actions of ketanserin.
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PMID:Alpha-adrenergic blockade makes minimal contribution to ketanserin's hypotensive effect. 290 12

In rats anaesthetized with urethane, increasing the activity of 5-hydroxytryptamine receptors or the level of cuntional serotonin in the brain with the inhibitors of the reuptake of serotonin, fluoxetine, produced both hypertension and tachycardia. The hypertension induced by fluoxetine was significantly inhibited by pretreatment of the animals with ketanserin (a serotonin receptor antagonist), by bilateral vagotomy, spinal transection or bilateral adrenalectomy. On the other hand, the tachycardia induced by fluoxetine was significantly inhibited by pretreatment with ketanserin or bilateral vagotomy, but not by spinal transection or adrenalectomy. The data indicate that fluoxetine acts through serotonin receptors in the central nervous system by influencing autonomic outflow to induce both hypertension and tachycardia.
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PMID:Hypertension and tachycardia produced by inhibition of reuptake of 5-hydroxytryptamine by fluoxetine in the rat. 294 28

Recently, the role of the serotonergic nervous system has been implicated in blood pressure regulation and in the pathogenesis of hypertension. However, the effects of 5-hydroxytryptamine (5-HT) administration on hemodynamics have been notoriously inconsistent and the precise mechanism of the blood pressure regulation of the serotonergic nervous system has not been elucidated yet. In our previous study, we demonstrated that the intracerebroventricular (i.c.v.) administration of 5-HT in rats elicited consistent pressor response with concomitant increase in plasma norepinephrine and that the pressor response was abolished by systemic pretreatment of phenoxybenzamine or by serotonin receptor antagonist, methysergide. The purpose of this experiment is to investigate further the relationship between the sympathetic nervous system and the serotonergic nervous system.
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PMID:[The role of the sympathetic nervous system and adrenals in hemodynamic changes after intracerebroventricular administration of 5-hydroxytryptamine in rats]. 308 42

In 41 patients with Primary Raynaud's Phenomenon (PRP) the effectiveness of the serotonin receptor blocker ketanserin has been studied in a double blind cross-over study. Subjective assessments included: frequency and duration of the attacks (both per se and combined to a severity score), cold sensation, numbness, paresthesia, pain, cold water and cold weather provocation and the appearance of spontaneous attacks. The objective measurements comprised Digital Skin Temperature (DST), Digital systolic Blood Pressure (DBP) and Doppler Spectral Analysis (DOSA) of the radial and ulnar arteries. All measurements were performed both at room temperature and after instant cold provocation. The severity score, the occurrence of numbness and paresthesia and cold weather provocation improved significantly on ketanserin treatment. All objective measurements with the exception of the end-diastolic blood flow velocity of DOSA did not show significant improvements. Neither blood chemistry nor systemic blood pressure showed any significant change during ketanserin treatment. However, in the 6 (15%) patients with hypertension both systolic and diastolic blood pressure normalized. Although in objective measurements hardly any significant effects of ketanserin could be demonstrated, the results of the study suggest that orally administered ketanserin is effective for minimizing subjective complaints in patients with PRP. Ketanserin did not show any side effects.
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PMID:The effectiveness of ketanserin in patients with primary Raynaud's phenomenon. A randomized, double blind, placebo controlled study. 332 7

Monotherapy with Ketanserin, a serotonin receptor antagonist, reduces blood pressure in a sizeable number of patients with essential hypertension. The present study was designed to compare its antihypertensive potency with those of metoprolol in a double-blind treatment and further to study its long-term efficacy and safety in a one-year open trial, alone or combined to metoprolol, according to diastolic blood pressure (DBP) normalization. Twenty-four patients with mild to moderate hypertension were randomly assigned to two parallel treatment groups, one group (n = 11) received Ketanserin (40 mg/day) and the other one (n = 13) metoprolol (200 mg/day). After 3 months double-blind treatment, all patients received Ketanserin, on an open basis for one year alone or combined to metoprolol if Ketanserin failed to normalize DBP. A significant antihypertensive effect was demonstrated after 3 months double-blind treatment, for Ketanserin and metoprolol, in both standing and supine position (p less than 0.01). Heart rate showed a clear decrease by metoprolol (p less than 0.01). In the one-year follow-up, patients were divided in: I (n = 7) patients on Ketanserin (previously treated with the same drug); II (n = 4) patients on Ketanserin plus metoprolol (previously treated with Ketanserin, in whom it failed to normalize DBP); and III (n = 13) patients on Ketanserin (previously treated with metoprolol). In group I the blood pressure lowering effect of Ketanserin remained constant after one-year follow-up. In group II, although the number of patients was insufficient, a trend in the decrease of parameters was observed. In group III, supine and standing DBP diminished from 92.5 +/- 8 and 92.5 +/- 7 during treatment with metoprolol to 83.6 +/- 9 and 79.8 +/- 8 mmHg respectively at 12 months, after treatment with Ketanserin (p less than 0.05); accordingly, the cumulative percentage of normalized DBP increased from 4/13 after metoprolol to 12/13 at the end of the trial. Ketanserin side effects were minimal. Taking into account the wide variety of contraindications or side effects with beta-blockers and diuretics, Ketanserin appears as a new and important alternative in the treatment of mild and moderate essential hypertension.
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PMID:Ketanserin in the treatment of essential hypertension. A double-blind study against metoprolol and a further long-term open treatment. 354 22

Ketanserin, a serotonin receptor antagonist (S2), lowered blood pressure in patients with essential hypertension; at three months 72% (13/18) had a successful reduction in pressure. No marked orthostatic changes were noted. Older patients responded better when standing. Compared with metoprolol, ketanserin provided no significant difference in response at three months. With ketanserin, the heart rate was reduced only in the supine position, whereas it was reduced in the supine and standing positions with metoprolol. Response to ketanserin could not be predicted from baseline renin, aldosterone, or cortisol levels in blood, nor were there any changes in these factors or in plasma hydroxyindole levels with therapy. Ketanserin was generally well tolerated. Cholesterol values were significantly reduced with ketanserin, and there were no adverse hematologic or biochemical changes. Ketanserin should have a significant role in managing hypertension.
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PMID:Comparison of ketanserin and metoprolol in the treatment of essential hypertension. 354 16


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