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

The antihypertensive efficacy of a receptor antagonist of serotonin was compared with a widely known antihypertensive drug, metoprolol, and their effects on cardiac and forearm hemodynamics were studied using echocardiography and flowmetry with pulsed bidimensional Doppler. Twenty patients with hypertension completed a randomized double-blind crossover study, using ketanserin and metoprolol. Two periods of 5 weeks with ketanserin or metoprolol were preceded by a placebo period the total duration of the study was 15 weeks. Although comparable efficacy in reducing systolic and diastolic pressure, (by about 10% of base-values), was observed, the two drugs showed quite different effects on forearm hemodynamics. Ketanserin increased blood flow to the forearm and induced a significant decrease in the vascular resistances of the forearm (from 141 +/- 16 to 75 +/- 11 mmHg/mL/s; p less than 0.01). Moreover, this treatment was able to improve the compliance of the brachial artery (from 1.89 +/- 0.3 to 3.2 +/- 0.3 cm4/dyn 10(-10); p less than 0.01). On the contrary, metoprolol did not modify forearm hemodynamics. Neither drug modified cardiac performance, as assessed by the circumferential shortening of the fibers of the left ventricle. Cardiac output was increased by ketanserin (from 5.9 +/- 0.3 to 6.6 +/- 0.5 L/min; p less than 0.05) and reduced during treatment with metoprolol (from 5.9 +/- 0.4 to 4.9 +/- 0.3 L/min; p less than 0.01). Thus the two drugs reduced arterial pressure by different hemodynamic mechanisms and the effects of ketanserin on systemic and peripheral circulation seem more favourable.
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PMID:[Effects of chronic antihypertensive treatment with ketanserin versus metoprolol on blood pressure and compliance of great arteries in man: a double-blind crossover study]. 210 34

Ketanserin is a specific antagonist of the 5-HT2 serotoninergic receptors; it is located on the smooth muscle cells of the vessel wall, and its stimulation causes vasoconstriction. The aim of this study is to evaluate the antihypertensive effect of ketanserin in patients with essential and secondary hypertension. Both systolic and diastolic blood pressure significantly decreased, in 18 patients, after chronic treatment with oral therapy (40-80 mg/day), and in 37 patients, after acute administration of sublingual (20 mg) and intravenous (10 mg) ketanserin. Acute administration of ketanserin was less effective than nifedipine (10 mg) in severe hypertension. Ketanserin, compared to placebo, permitted the normalization of blood pressure in 6/10 patients. Cardiovascular effects of ketanserin were studied with the ECOCG method in 8 patients with hypertension: peripheral resistances decreased, but left ventricular function and structure did not change. The effect of ketanserin on Na transmembrane transport systems in erythrocytes was studied both in vivo and in vitro, in order to evaluate the ketanserin action mechanism. The Na/K pump decreased and Na/Li countertransport increased, while different concentrations of serotonin did not change the transmembrane transport systems. In conclusion, ketanserin has a direct effect on transmembrane transport systems, not mediated by the serotonin receptors. This effect, with an antagonist of 5-HT2 serotoninergic and alpha 1 adrenergic receptor action, can cause a hypotensive effect.
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PMID:[Evaluation of acute and chronic effects of ketanserin in the treatment of hypertension and hypothesis on a new mechanism of action]. 210 30

The preeclampsia-eclampsia syndrome is a severe complication of the third trimester of pregnancy and represents the first cause of maternal death. It is mainly characterized by: weight increase, proteinuria and hypertension and can evolve with convulsions and maternal death. The etiology still remains unknown although a series of events have been identified, starting with endothelial damage and local vasoconstriction leading to hypertension. These events occur at first locally in the placental district and become generalized. This paper reports experimental and clinical data in order to demonstrate: 1) the presence of a substance that could evoke experimentally the damage present in this syndrome, 2) a mechanism that delivers such a substance to its primary action site, the placenta, and 3) the possibility to inhibit either the substance or the delivery mechanism in order to prevent this disease. Serotonin appears to play an important role in the chain of events leading to preeclampsia. Certain histological aspects, present in pregnant women with this type of hypertension, have been observed in experimental animals after the administration of serotonin. Platelet derived serotonin could be sufficient, in the case of endothelial damage, to determine vasospasm. In a condition of hypercoagulability, such as pregnancy, this situation can trigger a chain of mechanisms ending with renal damage. Low dose aspirin seems a valid therapeutic approach reducing thromboxane concentrations and therefore preventing vasospasm. In this way the pathogenetic sequence culminating in the preeclampsia-eclampsia syndrome is interrupted. Ketanserin inhibits the hypertensive potential of serotonin by selectively acting on S2 serotonin receptors and appears to be an effective treatment in this type of pregnancy induced hypertension.
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PMID:[Serotonin and hypertension in preeclampsia-eclampsia syndrome]. 210 37

Serotonin is a vasoactive amine. It is formed in the chromaffin cells in the small intestine and is inactivated in the liver and lungs. The remainder is taken up in the thrombocytes so that only minimal quantities are found free in the plasma. The peripheral effect of serotonin occurs probably exclusively by means of a release of amine from the thrombocytes following local aggregation of these. Serotonin is thought to play a pathogenetic role in both systemic and pulmonary hypertension. Ketanserin is a serotonin antagonist with alpha-blocking effect. It reduces the blood pressure by reducing the peripheral vascular resistance without causing reflex tachycardia or fall in the minute volume of the heart. In the field of anaesthesiology, it may be employed in per- and postoperative hypertension but on account of the peripheral vasodilating effect it may also be employed in other conditions with peripheral vasoconstriction. Ketanserin has a moderate effect in cases of acutely developed pulmonary hypertension.
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PMID:[Use of ketanserin in anesthesia. A selective S2 serotonin receptor antagonist]. 219 27

Lowering blood pressure is not totally effective in preventing the atherosclerotic complications of systemic hypertension. In hypertensive patients both platelet hyperaggregation and dyslipidemia have been suggested as important risk factors. The effect of 8 weeks' treatment with ketanserin on blood pressure, serum lipid parameters (cholesterol, triglycerides, LDL, HDL-C, apolipoprotein A1 and B) and platelet aggregation, induced by collagen, ADP, arachidonic acid, was evaluated in 10 patients with essential hypertension. Ketanserin was effective in lowering blood pressure in all patients, 6 of whom became normotensive. Both CHOL and TG levels and APO B were significantly reduced, whereas HDL-C and APO A1 were significantly increased after treatment. These results might be attributed to the antagonistic activity of ketanserin on alpha-1 adrenoceptors with a consequent inhibition of phosphodiesterase. Platelet aggregation, after stimulation with collagen and arachidonic acid, was significantly reduced secondary to the inhibition of intraplatelet serotonin synthesis and release. These results suggest that keranserin is effective in reducing blood pressure and in achieving normal serum lipid pattern and platelet aggregation. Therefore, this drug might be helpful in controlling the main risk factors for cardiovascular damage.
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PMID:Effects of ketanserin administration on lipid metabolism and platelet aggregation in hypertensive patients. 227 4

Ketanserin is the prototype of a new class of antihypertensive drugs based on a selective blockade of serotonin S2 receptors. A number of controlled trials have indicated that ketanserin is more effective in older than in younger subjects and that, in the elderly, ketanserin may be even more effective than other antihypertensive drugs. We set up a large multicenter trial to compare the two most common dosages of ketanserin (20 mg and 40 mg twice daily) in patients of 60 years of age and over. In these patients, blood pressures were elevated systolically (SBP greater than or equal to 160 mmHg), diastolically (DBP greater than or equal to 95 mmHg), or both, and any existing antihypertensive medication was continued at a constant dosage. The total duration of the trial was 3 months and monthly control visits were held. Throughout the Netherlands, 252 general practitioners participated in the trial, which included 462 evaluable patients. After 1 month of open treatment with 20 mg ketanserin twice daily, blood pressure was found to be fully normalized in 18% of patients, while the proportion of patients with both systolic and diastolic hypertension was reduced from 89% to 50%. In three out of four patients, an adequate and maximal fall in blood pressure was reached only after 2-3 months of treatment. In such patients, raising the ketanserin dose from 20 mg to 40 mg twice daily did not result in any faster or improved antihypertensive response. A number of symptoms related to peripheral circulatory disturbances, or possibly to hypertension itself, markedly improved during oral treatment with ketanserin.
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PMID:Oral dosing with ketanserin to control high blood pressure in the elderly. 228 39

The results of the European Working Party for Hypertension in the Elderly Study showed that treatment of high blood pressure reduced the morbidity and mortality from strokes and myocardial infarction and reduced the incidence of heart failure in elderly patients. The largest number of hypertensive patients are elderly, and it is in this group of patients that the maximum benefit of treatment might be expected. The present study was designed to study in detail the efficacy and tolerability of ketanserin in an elderly population. Seventeen elderly (greater than 70 years) patients with a lying systolic blood pressure of 160 mmHg and/or a diastolic blood pressure of greater than or equal to 90 mmHg were included in the study. For the 12 patients who completed the study, the mean blood pressure was significantly reduced on ketanserin compared with placebo (p less than 0.001) in the supine and erect positions. The mean net changes in blood pressure after 8 weeks were 21/17 mmHg and 23/16 mmHg erect. Heart rate was also significantly reduced (p less than 0.001) by a mean of 8 beats/min lying and 9 beats/min erect. Analysis of ambulatory 24-hour ECG tapes showed no significant effect of ketanserin on heart rhythms. Ketanserin therapy had no significant effect on routine hematology, plasma electrolytes, biochemistry, or urinalysis. Total exchangeable sodium and potassium and body weight were also unchanged. On ketanserin treatment, the overall quality of life score was significantly improved (p = 0.002; analysis of variance on log transformed data) compared with the placebo phase.
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PMID:A placebo-controlled crossover study of ketanserin in elderly hypertensive patients. 228 40

This study was performed in order to evaluate the effects of ketanserin monotherapy on blood pressure and glucose metabolism in essential hypertensives with type 2 diabetes. Twenty-nine patients, 17 males and 12 females, aged 45 to 78 years, with mild hypertension (DBP greater than or equal to 95 and less than or equal to 105 mmHg) and type 2 diabetes were studied. After a 4 week run-in period on placebo, each patient received ketanserin 20 mg b.i.d. for 6 months, with no modification in previous antidiabetic therapy. SBP, DBP, HR, fasting and post-prandial glycemia were monitored monthly. An oral glucose tolerance test (OGTT), glycosilated hemoglobin (HbA1c), urinary C-peptide, serum electrolytes, creatinine, uric acid, total cholesterol and 24 h protein and glucose urinary excretion were evaluated before and after 3 and 6 months of treatment. Ketanserin significantly reduced both SBP and DBP (p less than 0.005) with no changes in HR. No significant modifications of fasting and post-prandial glycemia, HbA1c and C-peptide were observed. Besides, ketanserin did not affect glucose tolerance, the levels of glucose during the OGTT were not significantly different before and after treatment. None of the patients required any change in antidiabetic therapy. In conclusion, ketanserin was effective in the treatment of mild hypertension in patients with type 2 diabetes. The absence of effects on glucose metabolism makes it an especially interesting drug in such patients.
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PMID:Ketanserin in chronic treatment of hypertension in type 2 diabetes mellitus. 236 39

The serotonin antagonist methysergide has a partial agonistic action on isolated vascular smooth muscle from hypertensive animals, whereas ketanserin, another serotonin antagonist, does not. The goal of this study was to determine the effects of these two agents on blood pressure in the conscious, deoxycorticosterone acetate (DOCA) hypertensive sheep. Adult sheep maintained on a standard laboratory diet and 0.1% NaCl/0.25% KCl drinking water developed hypertension following DOCA implantation (mean arterial pressure: control = 83 mm Hg, DOCA = 108 mm Hg). Methysergide (40 micrograms/kg--i.v. bolus) produced a greater pressor response in hypertensive sheep than in normotensive sheep (control = 8 +/- 1 mm Hg, DOCA = 18 +/- 3 mm Hg). Ketanserin (50 micrograms/kg--i.v. bolus), on the other hand, caused a similar decrease in blood pressure (approximately -16 mm Hg) in both control and DOCA sheep. Pressor responses to infusions of serotonin were greater in DOCA sheep compared with controls. Both methysergide and ketanserin were equally effective antagonists of a serotonin-induced pressor response (75% inhibition) in control and DOCA sheep. Methysergide had no effect on a norepinephrine-induced pressor response, but ketanserin caused a 20% attenuation of this response. These results demonstrate an enhanced responsiveness to serotonin and methysergide in DOCA hypertensive sheep.
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PMID:Effects of serotonin antagonists on blood pressure in mineralocorticoid hypertensive sheep. 241 Jul 5

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.
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PMID:Serotonergic mechanisms and blood pressure in sheep. 241 29


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