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

Ketanserin ia a quinazoline derivative which acts selectively on serotonin (S2) receptors. The compound has been shown to possess antihypertensive properties. BP and HR were measured blindly on 14 patients with essential hypertension during one year. Ketanserin 40 mg, once or twice daily, reduced BP (and HR to a slight extent) largely unchanged from 14 days after initiation of therapy. Response rate varied from 57-77% at the regular control visits. During the one year follow up period the reduction in supine SBP was 9 +/- 3% (p less than 0.001) and DBP was 12 +/- 1% (p less than 0.001). The only side effect was a slight sedation that passed with time. It is concluded that ketanserin is effective in the chronic treatment of hypertension and may offer a new alternative to existing pharmacotherapy.
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PMID:Experience with ketanserin, a serotonin (S2) antagonist, in longterm treatment of essential hypertension. 637 66

In patients developing hypertension following coronary artery bypass surgery (CABG) the possible role of 5-hydroxytryptamine (5-HT; serotonin) was investigated by injecting ketanserin, a specific 5-HT2-receptor antagonist. Ketanserin was administered intravenously when intraarterial systolic blood pressure (SAP) exceeded 150 mm Hg either as a 10-mg bolus (group 1, N = 15), or as a 10-mg bolus followed by infusion of 4 mg/h for either 2.5 h (group 2, N = 15) or for 1 h (group 3, N = 10). In 33 patients (82.5%), SAP and diastolic arterial pressure decreased significantly within 5 min after the 10-mg bolus. In group 1, SAP gradually increased after 30-50 min but in groups 2 and 3 SAP remained normal. The triple index (TI) decreased significantly in all groups. Heart rate decreased slightly but significantly in groups 2 and 3. Central venous and left atrial pressures did not change substantially in any of the three groups. Cardiac output increased significantly (0.51 +/- 0.158 L/min); hence, systemic vascular resistance (SVR) decreased significantly (452.1 +/- 50.57 dyn . s . cm-5--group 3). No rebound increase in SAP occurred after terminating the infusions (groups 2 and 3). These findings indicate that 5-HT plays a role in the majority of patients who develop hypertension following CABG. The decrease of SVR without reflex tachycardia is a favorable effect of ketanserin.
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PMID:The use of ketanserin, a 5-hydroxytryptamine receptor antagonist, for treatment of postoperative hypertension following coronary artery bypass surgery. 660 Mar 82

Ketanserin, a 5HT2-receptor blocking drug was given to 17 patients with essential hypertension. Satisfactory control was achieved in 13 patients. Control was not as satisfactory when given once daily. There was no rebound effect when the drug was ceased. Side-effects were few. Ketanserin was a satisfactory drug to reduce blood pressure in patients with moderate hypertension.
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PMID:The effect of ketanserin in essential hypertension. 662 48

Ketanserin is a new, specific serotonin receptor blocking agent, which causes vasodilatation, presumably by an action on the vascular wall. The antihypertensive response to ketanserin 40 mg twice daily as monotherapy was assessed in 8 patients with essential hypertension. The investigation was an 8 week, double-blind, cross over study, which also included measurements during isometric (handgrip) and dynamic exercise (bicycle ergometry), as well as determination of plasma catecholamines and ketanserin. Ketanserin caused a reduction of supine and standing systolic and diastolic blood pressure (BP) during rest and a slight bradycardia. Although there was attenuation of the pressor response to handgrip, treatment with ketanserin did not really affect the changes in BP or heart rate during exercise, i.e. the base-line differences remained the same. There was no significant correlation between the effect on BP and the plasma level of ketanserin. The changes in BP produced by ketanserin showed little correlation with the initial levels of plasma catecholamines or with alterations in those levels. Although the results did not indicate direct interference by ketanserin with sympathetic tone, the lack of reflexogenic tachycardia, as well as the lack of increase in plasma noradrenaline during hand grip, indicates at least some modulation of autonomic function. It is concluded that ketanserin lowers BP in essential hypertension without interference with cardiovascular reflexes during standing or exercise, and that the compound may offer an alternative approach in the treatment of hypertension.
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PMID:Ketanserin in essential hypertension: effects during rest and exercise. 662 17

The role of alpha 1-adrenoceptors in the hypotensive response to ketanserin was studied in conscious normotensive (sham-operated) and Page hypertensive (two-kidney, two wrapped) rabbits. Ketanserin (0.01, 0.1 and 1 mg/kg i.v.) was administered at 30 min intervals on four experimental days: no pretreatment; after prazosin 1 mg/kg and infusion; after pharmacological 'total' autonomic effector block (TAB) and with repeated three point methoxamine dose-response lines. Only the highest dose (1 mg/kg) of ketanserin lowered blood pressure and dilated the iliac vascular bed (Doppler flowmeter) in both wrap and sham-operated rabbits. Prazosin pretreatment and TAB prevented these effects. Ketanserin (1 mg/kg) also caused significant alpha 1-adrenoceptor antagonism as measured by a 2.5-fold shift in the methoxamine dose-response lines. In separate experiments prazosin (0.01-0.1 mg/kg i.v. bolus) caused similar falls in blood pressure and alpha 1-adrenoceptor block as ketanserin 0.3 and 1 mg/kg. The only difference observed between prazosin and ketanserin was the substantial reflex tachycardia to prazosin that was absent after ketanserin. These results suggest that in normotensive rabbits and in rabbits with Page hypertension the hypotensive response to ketanserin can be explained by alpha 1-adrenoceptor antagonism.
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PMID:Haemodynamic response to ketanserin in rabbits with Page hypertension: comparison with prazosin. 668 Oct 38

Vascular responsiveness to 5-hydroxytryptamine (5-HT) is dramatically increased in hypertension. The hypothesis that augmented vasoconstriction to 5-HT in hypertension is due to a change in receptor subtype on vascular myocytes was tested. Mesenteric arteries from deoxycorticosterone acetate (DOCA)-salt hypertensive (systolic blood pressure > 180 mm Hg) and sham normotensive (systolic blood pressure < 130 mm Hg) rats were mounted in isolated tissue baths for measurement of isometric contractile force. The receptor mediating contraction in isolated mesenteric arteries from sham and DOCA-salt hypertensive rats is a member of the 5-HT2 family based on rank order of agonist potency (5-HT = alpha-methyl-5-HT [5-HT2 receptor agonist]>tryptamine>5-hydroxykynuramine). 5-HT was approximately 10-fold more potent in contracting mesenteric arteries from DOCA-salt hypertensive rats compared with arteries from sham normotensive rats. The tryptophan metabolite kynuramine, which possesses significant contractile activity at the 5-HT2B receptor, contracted hypertensive arteries significantly (50% of 5-HT maximum) but not sham arteries. Ketanserin (5-HT2A antagonist) competitively inhibited contraction to 5-HT in arteries from normotensive rats (-log dissociation constant [mol/L]; pKB = 8.54) but not from hypertensive rats (pKB > 6.5). Moreover, contraction to kynuramine was not blocked by ketanserin. Thus, under normal conditions, 5-HT2A receptors mediate contraction to 5-HT. However, in DOCA-salt hypertension, ketanserin-insensitive 5-HT2 receptors, possibly 5-HT2B receptors, mediate mesenteric arterial contraction to 5-HT.
Hypertension 1995 Dec
PMID:5-Hydroxytryptamine2B receptor mediates contraction in the mesenteric artery of mineralocorticoid hypertensive rats. 749 67

Serotonin, or 5-hydroxytryptamine, is a naturally-occurring vasoactive substance found primarily in the brain, enterochromaffin tissue, and blood platelets. It has diffuse cardiophysiologic effects. The multiple effects of serotonin on blood vessels can be explained by the existence of 2 serotonergic receptor subtypes (the S1 receptor mediates vasodilation, and the S2 receptor vasoconstriction). Serotonin via the S2 receptor also augments the actions of several other vasoconstricting substances. Serotonin may be responsible for causing, or at least perpetuating, some forms of systemic hypertension through peripheral and central nervous system (CNS) actions. Ketanserin is a highly selective S2-serotonergic antagonist with additional alpha-adrenergic blocking activity, which has been proposed as a therapy for various cardiovascular diseases including hypertension. It has been shown to be more effective than placebo in treating hypertension and comparable in effectiveness to other antihypertensive drugs. Its major side effects relate to the CNS, and prolongation of the electrocardiogram QT interval has been described. Caution must be used when using ketanserin in patients receiving potassium- and magnesium-losing agents, because of the risk of torsades de pointes. Ketanserin has potential utility in the treatment of eclampsia, peripheral vascular disease, carcinoid syndrome, and "shock lung." The drug is not yet approved for clinical use in the United States.
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PMID:Serotonin and serotonin antagonism in cardiovascular and non-cardiovascular disease. 766 16

The prevalence of hypertension increases with age. Multiple physiologic factors are involved in the development of hypertension in the elderly. Alpha1-adrenergic blocking agents lower blood pressure through a reduction in total peripheral resistance. Prazosin, terazosin, and doxazosin have been shown to be equally effective in reducing blood pressure in older persons. The bioavailability, terminal elimination half-life, and volume of distribution of prazosin is increased in the elderly. Hybrid drugs, such as ketanserin, urapidil, and indoramin are also effective in lowering blood pressure. Ketanserin seems to have a greater effect on blood pressure reduction in persons older than 60 years of age. Alpha1-adrenergic blockers may be used safely in patients with diabetes, asthma, and hyperlipidemia.
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PMID:Antihypertensive therapy in the geriatric patient: II. A review of the alpha1-adrenergic blocking agents. 809 84

The hypotensive action of ketanserin in humans remains incompletely defined but may be mediated by factors unrelated to vascular alpha 1 or serotonin2-receptor blockade. We examined the effects of ketanserin on indices of sympathetic drive, alpha 1- and serotonin2-receptor responses, and sympathetic tone in 13 elderly men with mild hypertension. Studies were performed after ten days and six weeks of double-blind assignment to placebo and ketanserin 40 mg twice daily. An eight week long single-blind, placebo washout period separated the double-blind phases. In the entire group, ketanserin lowered BP and heart rate significantly after six weeks but not at ten days. In contrast, plasma noradrenaline, an index of sympathetic drive, and platelet aggregation in response to 1 microM serotonin, an index of serotonin2-receptor antagonism, declined significantly after both ten days and six weeks (P < 0.05) on ketanserin versus placebo. Mean BP after six weeks on ketanserin fell to > 10% in seven patients (responders) and to < 10% in six subjects (nonresponders). Responders had higher baseline SBPs and heart rates compared with nonresponders. Even in responders, BP was reduced at six weeks but not after ten days on ketanserin versus placebo. Plasma and platelet noradrenaline, plasma renin activity, and platelet responses to serotonin at baseline and during ketanserin did not distinguish between responders and nonresponders. Ketanserin reduces sympathetic drive and antagonizes serotonin2-receptors in the short term. The relationship of these actions to the hypotensive effect of ketanserin, which is delayed and dependent on the initial BP, is unclear.
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PMID:Ketanserin's sympatholytic and serotonin2-receptor blocking actions precede the hypotensive effects. 815 8

The 5-HT2-receptor antagonist ketanserin (20-40 mg b.i.d.) was administered to 62 patients of both sexes with uncomplicated primary hypertension. After 4 weeks of treatment about 50% of the patients had reached the target diastolic blood pressure of 90 mm Hg or below. Interindividual variability was large. In a retrospective analysis the variability could not be explained by sex or the dose of ketanserin. There was a weak association between age and systolic blood pressure response (r = 0.24; P = 0.06), which could be entirely accounted for by the higher base line blood pressure in the elderly patients. In one group of patients (n = 12), the ex vivo aggregation to serotonin (10(-6) M) was studied during treatment with placebo and ketanserin. Ketanserin completely inhibited 5-HT-induced aggregation in all patients. There was a close correlation between the area under the 5-HT-induced platelet aggregation curve during placebo and the subsequent reduction in diastolic blood pressure after 4 weeks of treatment with ketanserin. The present data suggest that the blood pressure response to ketanserin can be predicted from the ex vivo sensitivity of platelets to serotonin. By implication, they also support a role for serotonergic mechanisms in hypertension.
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PMID:Serotonin-induced platelet aggregation predicts the antihypertensive response to serotonin receptor antagonists. 845 57


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