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

One of the most important problems during cardiac surgery is the prevention and treatment of hypertension, occurring in 40-60% of the patients following coronary artery bypass surgery (CABS). Hypertension should be avoided to prevent myocardial damage, neurologic complications, increased blood loss, and premature graft closure due to intimal damage. During and following cardiac surgery hypertension is routinely treated with vasodilating agents, which generally induce reflex tachycardia and increased intrapulmonary shunting. The results obtained with ketanserin, a specific S2-serotonergic receptor blocker with alpha 1-adrenergic receptor blocking properties, in the prevention and treatment of hypertension in patients undergoing cardiac surgery, are presented. Ketanserin effectively lowers blood pressure by decreasing systemic vascular resistance but does not completely prevent perioperative and postoperative hypertension when administered as a continuous infusion from the start of anesthesia. In contrast to sodium nitroprusside, ketanserin does not induce reflex tachycardia in the treatment of postoperative systemic hypertension following CABS. The compound improves diuresis and perfusion of the skin perioperatively. Ketanserin is devoid of rebound phenomena after its administration is stopped. It is postulated that the antihypertensive effect of ketanserin can be explained by its property of simultaneously blocking alpha 1-adrenergic and S2-serotonergic receptors.
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PMID:Ketanserin in the treatment of systemic hypertension during and following coronary artery bypass surgery. 251 May 60

Hypertension may accelerate the development of the vascular complications of diabetes but many conventional antihypertensive agents have adverse effects on glucose tolerance or peripheral perfusion. To investigate the potential of ketanserin as an antihypertensive agent for hypertensive diabetics we performed a randomly allocated, double-blind, placebo-controlled trial in 17 patients. A range of peripheral blood flow responses was determined using laser Doppler flowmetry, and diabetic control was assessed at the time of allocation to groups and after 8 weeks' therapy (20 mg twice a day for 2 weeks; 40 mg twice a day for 6 weeks). The mean decrease in standing blood pressure was 14.1/9.3 mmHg (ketanserin treatment) versus 7.1/5.9 mmHg (placebo). The maximum skin blood flow and a posturally induced vasoconstriction of the foot skin were unaffected by the therapy, and glycaemic control was unchanged. Ketanserin was well tolerated. These studies suggest that ketanserin may be a useful agent for the treatment of hypertension in the diabetic patient.
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PMID:An evaluation of ketanserin therapy for the hypertensive diabetic patient. 269 47

This study was carried out to investigate the hypotensive mechanisms of ketanserin and Ca-antagonists (verapamil and diltiazem) in hypertension. Perfused mesenteric vasculatures were prepared in spontaneously hypertensive rats (SHR, Okamoto and Aoki strain) and age-matched Wistar Kyoto rats (WKY), and the effects of these drugs on vascular responsiveness and norepinephrine release from the sympathetic nerve endings were examined. Pressor responses and endogenous norepinephrine release during periarterial nerve stimulation were significantly increased in SHR compared with age-matched WKY. Ketanserin, verapamil and diltiazem inhibited the stimulation-evoked pressor responses and norepinephrine release dose-dependently, respectively. The suppressive magnitudes of these responses by ketanserin, verapamil and diltiazem were greater in SHR than in WKY. The results demonstrate that ketanserin, verapamil and diltiazem might inhibit norepinephrine release from the vascular adrenergic neurons more strongly in hypertension. This sympatho-depressive effect may contribute, at least partially, to the hypotensive mechanisms of these antihypertensive drugs.
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PMID:Effects of ketanserin, verapamil and diltiazem on vascular sympathetic nerve activity in hypertension. 274 4

In a double-blind, placebo controlled study ketanserin, a serotonin S2 antagonist, was administered to hypertensive patients who had undergone coronary artery bypass surgery. Patients were allocated randomly to receive placebo or ketanserin at an infusion rate of 0.05, 1 or 2 mg kg-1 h-1. Sodium nitroprusside was used as escape medication. Ketanserin reduced the nitroprusside requirements and improved the quality of arterial pressure control in all groups, and this was significant in the low- and high-dose groups. There was a significant decrease in heart rate in the low- and high-dose groups compared with placebo, and no effect in patients who received the medium dose of ketanserin. Ketanserin may be a useful treatment for hypertension following coronary artery surgery as it reduced arterial pressure without reflex tachycardia.
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PMID:Effect of ketanserin on sodium nitroprusside requirements, arterial pressure control and heart rate following coronary artery bypass surgery. 278 22

The local hemodynamic effects of serotonin (5-hydroxytryptamine; 5-HT) and the selective 5-HT2 antagonist ketanserin were investigated in the forearm of 20 healthy volunteers. Single doses of 5-HT (0.1-80 ng/kg/min) and ketanserin (5-125 ng/kg/min) were administered intra-arterially. The relative alpha 1-adrenergic receptor and 5-HT2 blocking potencies of ketanserin were investigated using intra-arterial infusions of cumulative doses of methoxamine (0.1, 0.3, and 0.5 microgram/kg/min), tyramine (0.25, 0.50, and 1.25 microgram/kg/min), and 5-HT (10, 30, and 80 ng/kg/min) together with a low dose (5 ng/kg/min) and a high dose (50 ng/kg/min) of ketanserin. Forearm blood flow was measured by venous occlusion plethysmography. Heart rate and intra-arterial blood pressure were recorded semicontinuously. Intra-arterial infusion of 5-HT induced an initial transient vasodilatation, followed by a steady vasodilatation for the low doses of 5-HT (0.1-10 ng/kg/min; p less than 0.05). A steady vasoconstriction was only obtained at the highest dose of 5-HT. Ketanserin induced a dose-dependent increase in forearm blood flow from 15 ng/kg/min (p less than 0.05) onward. The vasodilatation induced by 5-HT (1 ng/kg/min) was significantly enhanced by ketanserin (125 ng/kg/min; p less than 0.05), whereas the vasoconstriction elicited by 5-HT (80 ng/kg/min) was reversed by ketanserin (50 ng/kg/min; p less than 0.05), thus confirming that 5-HT2 receptors were stimulated by 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1988 Mar
PMID:Regional vascular effects of serotonin and ketanserin in young, healthy subjects. 283 28

Ketanserin reduces blood pressure effectively, but without inducing tachycardia. Its precise mode of action is unclear but under some circumstances it attenuates the rise in blood pressure caused by infusion of the alpha 1-agonist phenylephrine, suggesting that it acts at least partly as an alpha 1-adrenoceptor antagonist. However, the specificity of this attenuation has been questioned. We have therefore examined the effects of ketanserin on the blood pressure and heart rate responses to angiotensin II (a vasoconstrictor agent largely devoid of alpha 1-agonist properties). The blood pressure response to infused angiotensin II, in contrast to that of phenylephrine, was not attenuated by ketanserin. Ketanserin appeared not to increase cardiac efferent parasympathetic activity. At a dose used in the treatment of hypertension, ketanserin produces alpha 1-antagonism in man, which may partly explain its antihypertensive effect.
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PMID:Specificity of the serotonergic antagonist ketanserin. 285 2

Using the radioactive microsphere technique, we studied the systemic and regional hemodynamic effects of ketanserin in conscious renal hypertensive rabbits. To characterize the hypotensive mechanism of the compound, we evaluated its antagonism toward 5-hydroxytryptamine2 and alpha 1-adrenergic receptors at hypotensive doses and compared the cardiovascular profile of ketanserin with that of the alpha 1-selective adrenergic receptor antagonist prazosin. Ketanserin (0.1, 0.3, and 1.0 mg/kg i.v.) produced a biphasic effect on the arterial blood pressure. A short, pronounced fall in blood pressure accompanied by tachycardia preceded a more moderate and longer lasting dose-related hypotensive effect. The presence of adequate autonomic nervous system activity seems to be required for the prolonged hypotensive action of ketanserin because, in animals pretreated with hexamethonium (30 mg/kg), the blood pressure, after an initial decrease, returned to baseline values within a few minutes after each ketanserin dose. Ketanserin inhibited the pressor responses produced by 5-hydroxytryptamine (10, 30, and 100 micrograms/kg i.v.) and phenylephrine (3, 10, and 30 micrograms/kg i.v.), which indicates that, at hypotensive doses, the compound antagonized both 5-hydroxytryptamine2 receptors and alpha 1-adrenergic receptors. At doses that caused a comparable degree of alpha 1-adrenergic receptor blockade, ketanserin (0.1, 0.3, and 1.0 mg/kg i.v.) as well as prazosin (0.01, 0.03, and 0.10 mg/kg i.v.) decreased the blood pressure as a result of a reduction in total peripheral resistance. While cardiac output increased, especially at the lower doses of ketanserin, a moderate decrease in this variable contributed to the hypotensive effect of the highest dose of prazosin. Both compounds decreased the vascular resistance in the kidneys, gastrointestinal tract, and bones, whereas that in the skin and skeletal muscles was not significantly altered. In contrast to prazosin, ketanserin also caused vasodilatation in the coronary and cerebral vascular beds.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension
PMID:Cardiovascular profile and hypotensive mechanism of ketanserin in the rabbit. 286 Nov 61

1. Ketanserin or slow-release nifedipine were added to the treatment of 24 patients with hypertension uncontrolled by a thiazide diuretic plus beta-adrenoceptor antagonist in an observer-blind, randomised parallel-group study of 6 months duration. 2. At 6 months the mean falls in supine blood pressure were for ketanserin (mean daily dose 77 mg) 7/5 mm Hg and for nifedipine (mean daily dose 62 mg) 27/10 mm Hg. The difference between the treatments was significant for systolic blood pressure (P less than 0.02) and mean arterial pressure (P less than 0.05). Six nifedipine-treated patients reached target blood pressure, compared with one patient with ketanserin (P less than 0.02). 3. One patient taking nifedipine, and none taking ketanserin withdrew because of side-effects. The tolerability of the two drugs was broadly similar. 4. Ketanserin treatment was associated with significant changes in supine pulse rate (-8 beats min-1, P less than 0.05) and corrected QT interval (+27 ms, P less than 0.05). Nifedipine treatment had no effect on these variables. The change in pulse rate was significantly different between the groups. 5. In patients treated with a diuretic and beta-adrenoceptor blocker who required additional treatment ketanserin was significantly inferior to nifedipine.
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PMID:Comparison of ketanserin and slow-release nifedipine added to the treatment of hypertensive patients uncontrolled by a thiazide diuretic plus beta-adrenoceptor blocker. 289 36

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

The safety and efficacy of ketanserin, a competitive serotonin blocking agent, and propranolol were compared in 33 patients with mild to moderate hypertension (sitting diastolic blood pressure [DBP] 95-115 mm Hg) using a placebo run-in, randomized, double-blind parallel study design. All patients received placebo for 4 weeks, then were randomized to receive increasing doses of either ketanserin (20, 40 mg twice daily) or propranolol (40, 80 mg twice daily) to achieve a goal sitting DBP less than 90 mm Hg. Patients not achieving the goal blood pressure with either drug as monotherapy, received the other drug in combination. At the end of the active monotherapy phase (week 10 of the study), propranolol demonstrated a greater decrease in DBP from baseline, as compared to ketanserin (-7.9 +/- 10.9 mm Hg with propranolol, P less than 0.05; -1.0 +/- 7.2 mm Hg with ketanserin, P = NS). Four out of 16 patients achieved goal response on propranolol, compared to 3/17 for ketanserin. With combination treatment, 9/18 patients reached the goal response; the addition of propranolol to ketanserin in non-responders resulted in further reduction of sitting DBP of -10.3 +/- 6.3 compared to monotherapy (P less than 0.001), while the addition of ketanserin to non-responders produced no significant response in sitting DBP. Propranolol showed a consistent effect in slowing heart rate. Ketanserin displayed less frequent side effects than propranolol. Propranolol used twice daily appears to be more effective than twice daily ketanserin use in patients with mild to moderate hypertension.
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PMID:Serotonergic blockade compared with beta-adrenergic blockade in systemic hypertension: a double-blind comparison of ketanserin with propranolol. 290 19


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