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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of serotonin and its pharmacological antagonists on the physical flow properties of the blood have been studied far less than their effects on blood vessels, although they may be equally important. Indirect evidence suggests that in pathological circumstances serotonin may locally increase whole blood viscosity, particularly at low shear rates, decrease red cell deformability and increase the adhesiveness of white cells. Although the viscosity of the plasma alone is not affected, the rheological effects of serotonin on blood cells is probably dependent on the presence of platelets. These mechanisms may have a systemic effect in some forms of hypertension as well as in situations of local ischaemia such as Raynaud's phenomenon, atherosclerotic pregangrene of the leg or acute myocardial infarction. Specific serotonergic-antagonists, administered either orally or intravenously, normalize the increased whole blood viscosity and decreased blood filterability found in essential hypertension, following myocardial infarction and in severe leg ischaemia. The effect on red cell deformability is usually greatest when the cells are resuspended in platelet rich plasma. Ketanserin given intravenously for seven days to patients with very severe leg ischaemia, significantly improves whole blood viscosity, increases red cell transit time and most dramatically decreases pore clogging. This last effect was at least partly due to a change in the physical properties, but not the number of the white cells. The reported beneficial clinical effects of such an antagonist in various forms of peripheral ischaemia and essential hypertension may well be due, at least partly, to the normalization of the rheological properties of the blood.
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PMID:Serotonin and the flow properties of blood. 241 54

In the Swiss Ketanserin Study the antihypertensive efficacy and tolerability of ketanserin (given in 20 or 40 mg doses twice daily) was investigated, after a placebo run-in phase, as monotherapy (n = 68) as well as in combination with either atenolol (100 mg/day) (n = 30) or the potassium-sparing diuretic hydrochlorothiazide (50 mg/day) and amiloride (5 mg/day) (n = 26) in 124 patients with essential hypertension, aged 41 to 82 years. With the addition of ketanserin, diastolic blood pressure fell by 8 +/- 8, 8 +/- 8, and 7 +/- 9 (+/- SD) mm Hg, respectively (p less than 0.05 for all) in the three treatment groups; heart rate remained unchanged or fell slightly. Ketanserin had no effect on body weight, or biochemical variables, including total serum cholesterol and triglycerides, with the exception of a minor increase in apolipoprotein B. Using a patient self-assessment questionnaire (30 items), the addition of ketanserin was associated with a reduction of most of the symptoms encountered in the placebo phase, including sleep disturbances, general feeling of weakness, headaches, nervousness, and fatigue, but there was a tendency toward increases in stuffy nose and dry mouth. In patients older than 60 years, the antihypertensive efficacy of ketanserin was greater, with 59% achieving a diastolic pressure less than or equal to 95 mm Hg versus 45% in the younger patients. This age trend also emerged when ketanserin was combined with either atenolol or the diuretic.
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PMID:Antihypertensive efficacy of ketanserin alone or in combination with a beta-blocker or a diuretic: the Swiss Ketanserin Study. 244 58

It remains to be established whether ketanserin's antihypertensive effect is caused by S2-serotonergic blockade, by alpha 1-adrenergic blockade, or by a combination of both. Ketanserin, 10 mg i.v. or 40 mg t.i.d. orally, blocked the serotonin-induced contractions of hand veins in patients with essential hypertension. Intravenous ketanserin had no effect on the venoconstrictor action of noradrenaline. The increase in digital blood flow after i.v. ketanserin, as measured by the change in digital skin temperature in patients with Raynaud's phenomenon, was not blocked by phentolamine or pretreatment with prazosin. Intravenous ketanserin also lowered arterial pressure in patients with autonomic insufficiency who were unresponsive to phentolamine. These observations suggest that alpha-adrenergic blockade is not the sole mechanism of ketanserin's cardiovascular actions in humans.
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PMID:Role of alpha-adrenergic blockade in the cardiovascular actions of ketanserin: studies in patients with essential hypertension, autonomic insufficiency, and Raynaud's phenomenon. 244 64

In patients with essential hypertension, an activated platelet serotonin-induced vasoconstrictor axis can be postulated. Platelets from hypertensive patients have a shortened half-life, and turnover of serotonin is increased. Vasoconstriction may be produced through activation of 5-HT2 receptors secondary to high wall concentrations of serotonin released from "activated" platelets. The pharmacotherapeutic relevance of this pathophysiological chain of events can be tested with the 5-HT2-receptor blocker ketanserin, but the drug's alpha 1-blocking activity has to be taken into account. Ketanserin lowers blood pressure effectively and to a greater extent in older patients. This points to an age-linked mode of action, possibly related to greater endothelial and blood vessel damage with older age.
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PMID:Serotonin and preactivated platelets in essential hypertension. 244 66

Ketanserin is an arteriolar vasodilator, acting on serotoninergic (5-HT2) and adrenergic (alpha 1) receptors. In animals, ketanserin exerts a centrally mediated inhibition of sympathetic nerve activity. In humans it is not established whether ketanserin reduces basal or reflex increases in sympathetic outflow. In different groups of patients, we have investigated the cardiovascular response as well as plasma noradrenaline (pNA) during rest, during the cold pressure test (0 degree C for 3 min), and during isometric (handgrip), and/or dynamic exercise in order to see whether ketanserin reduces the normal increase in sympathetic tone during these maneuvers. Twenty-one patients with essential hypertension were given oral ketanserin (40 mg) once or twice daily for 4 weeks after a 2-4-week single-blind control period. Ketanserin significantly lowered systolic and diastolic blood pressure as well as heart rate during rest. Resting pNA was not significantly reduced, but the change in pNA was significantly correlated to the reduction in blood pressure and heart rate. During exercise, blood pressure and heart rate remained reduced. Moreover, the relative increase in systolic blood pressure during handgrip and the relative increase in heart rate during bicycle ergometry were significantly reduced during ketanserin therapy. During isometric exercise the relative reduction in blood pressure was significantly correlated to the relative reduction in pNA.
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PMID:Cardiovascular effects of ketanserin during cold pressure and during isometric and dynamic exercise in hypertensive patients. 244 77

Ketanserin is a novel agent that has been shown to be a specific 5-HT2-serotonergic antagonist. It has useful antihypertensive properties. Owing to its unique mechanism of action, it has been suggested that ketanserin may have a favorable effect on tissue blood flow during chronic therapy for hypertension. This double-blind study was designed to evaluate the acute (1 week) and chronic (8 weeks) effects of ketanserin on renal hemodynamic parameters and renin-aldosterone axis in patients with uncomplicated hypertension. Compared to placebo, ketanserin caused a significant blood pressure reduction at the end of the 8-week study period. Despite the reduction in systematic arterial pressure, glomerular filtration rate and renal plasma flow were preserved. Ketanserin therapy induced a slight reduction in plasma renin activity and a marginal increase in the sodium excretion. Although the results of this study are limited by the small number of patients, it appears that ketanserin may have favorable renal hemodynamic effects in uncomplicated essential hypertension.
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PMID:Renal hemodynamic effects of ketanserin therapy in essential hypertension. 244 78

We have studied the acute effects of the serotonergic type-2 (5-HT2) antagonists ketanserin and ritanserin given as single oral doses to patients with essential hypertension. Ketanserin has alpha 1-antagonist properties, whereas ritanserin is largely devoid of alpha 1-receptor binding affinity. Ketanserin (40 mg orally) caused a significant reduction (p less than 0.03) of sitting mean arterial pressure over the 8-h period following drug administration by an average of 15.4 +/- 3.2 mm Hg (mean +/- SEM) as compared to a reduction of 8.5 +/- 2.2 following placebo. In contrast, ritanserin had no significant effect on blood pressure compared to placebo; sitting mean arterial pressure was reduced by 9.0 +/- 2.6 and 10.8 +/- 1.8 mm Hg after administration of 10 and 20 mg, respectively, of ritanserin. There were no significant differences in pulse rate among placebo, ketanserin, or ritanserin phases. Ritanserin caused a reduction in the hostility score (p less than 0.05) as measured by the Multiple Affect Adjective Check List; ketanserin had no significant effects. The highly selective 5-HT2 antagonist ritanserin, given in a dose which caused measurable alteration of psychological function tests, had no acute effects on blood pressure. The acute antihypertensive effects of ketanserin are not caused by 5-HT2 antagonism alone, but are likely to be dependent on its alpha 1-antagonistic properties.
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PMID:Does acute serotonergic type-2 antagonism reduce blood pressure? Comparative effects of single doses of ritanserin and ketanserin in essential hypertension. 244 81

This study assesses the efficacy, safety, and dose-response curve of ketanserin, according to parenteral routes of administration, in the treatment of acute severe essential hypertension. We studied 50 patients with supine diastolic blood pressure (SDBP) phase V greater than or equal to 110 mm Hg after 2 h of continuous BP monitoring. Ketanserin was administered as follows: 5 mg i.m. (Group I: SDBP X = 115.7 mm Hg); 10 mg i.m. (Group II: SDBP X = 119.0 mm Hg); 5 mg i.v. (Group III: SDBP X = 123.9 mm Hg); and 10 mg i.v. (Group IV: SDBP X = 130.8 mm Hg), according to initial severity of symptoms and BP. All patients were monitored, and most of them were on antihypertensive treatment. [Total group mean age: 57.9 years (range: 38-78 years)]. There were 35 men and 15 women. Systolic BP fell progressively, from a mean of 177.9 mm Hg (basal) to 156.4 mm Hg at 60 min postadministration (Group I), p less than 0.01; from 188 to 164 mm Hg (Group II), p less than 0.05; from 192.1 to 157.9 mm Hg (Group III), p less than 0.01; and from 207.5 to 168.3 mm Hg (Group IV), p less than 0.01). SDBP decreased from a basal mean value of 115.7 to 92.1 mm Hg at 60 min (Group I), p less than 0.01; from 119.0 to 98 mm Hg (Group II), p less than 0.05; from 123.9 to 101.6 mm Hg (Group III), p less than 0.01; and from 130.8 to 105.8 mm Hg (Group IV), p less than 0.01. Heart rate decreased slightly in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ketanserin in parenteral treatment of acute essential hypertension: a dose-response curve. 244 83

Concentrations of serotonin and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in platelet rich plasma, the urinary 5-HIAA excretion rate, and serotonin-induced platelet aggregation were measured in 17 patients with essential hypertension before, and at the end of, 8 weeks of oral ketanserin therapy at 20 to 40 mg twice daily. Ketanserin lowered systolic and diastolic blood pressure (p less than 0.01) and led to a reduction of serotonin concentration in platelet rich plasma in all patients (p = 0.05), as well as a decrease in 5-HIAA excretion rates in patients older than 55 years (p less than 0.05). Changes in 5-HIAA concentration in platelet rich plasma correlated with the fall in diastolic blood pressure (r = 0.67, p less than 0.05). Serotonin-induced platelet aggregation was inhibited by ketanserin (p less than 0.05), and this was more pronounced in older patients. Thus, antihypertensive therapy with ketanserin reduced platelet aggregation and serotonin metabolism in relation to the age of patients, and this may contribute to the reduction of their elevated rates of thromboembolic complications.
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PMID:Serotonin metabolism and age-related effects of antihypertensive therapy with ketanserin. 246 92

The present study was designed to compare the antihypertensive potencies of ketanserin and metoprolol in a double-blind trial and to study ketanserin long-term efficacy in a one-year open trial, plain or combined with metoprolol, according to diastolic blood pressure (DBP) normalization. Thirty-four patients were randomly assigned to two groups, one (n = 17) received ketanserin, 80 mg/day, and the other, (n = 17) metoprolol, 200 mg/day. After 3 mo. double blind treatment, all patients received plain ketanserin, or combined with metoprolol if ketanserin failed to normalize DBP. A significant effect was demonstrated after 3 mo. double blind treatment, for both drugs, in both standing and supine DBP (p less than 0.001). In the one-year follow-up, all patients received ketanserin and were divided in: I (n = 15) previously treated with the same drug; II (n = 2) plus metoprolol, in whom ketanserin had failed to decrease DBP; and III (n = 15) previously treated with metoprolol. In group I the blood pressure lowering effect of ketanserin remained constant during the one-year follow-up. In group II a trend in the decrease of parameters was observed. In group III, supine DBP diminished from 92.5 +/- 2 mmHg during treatment with metoprolol to 86.0 +/- 2 at 12 mo., after treatment with ketanserin (p less than 0.05). In groups I and III, 24/30 of patients normalized their DBP during one-year ketanserin open treatment. Ketanserin appears as a new 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 trial against metoprolol followed by one-year open treatment. 266 39


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