Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ketanserin, an antagonist of 5-HT2-serotonergic and alpha 1-adrenergic receptors, has come into use for the therapy of mild to moderate arterial hypertension. Quite recent observations have shown changes in transmembrane sodium (Na) transport after the acute administration of high doses of this drug to normal subjects. It is well known that some of these transport systems have an altered activity in essential hypertension. We evaluated the effects of long-term (3 months) administration of ketanserin (40-80 mg/day) on Na and potassium (K) intracellular concentrations and transmembrane fluxes in red blood cells (RBCs) from 12 essential hypertensive patients. In addition the present study describes the in vitro effects of two different concentrations of the drug (5 x 10(-8) and 5 x 10(-7) M) on erythrocytes in normal subjects. In the first study, both systolic and diastolic blood pressure were significantly lowered by the treatment with ketanserin (from 165/103 to 143/89; p less than 0.001). Na and K intraerythrocyte concentrations fell markedly during ketanserin administration (both p less than 0.001). A marked decrease in Na,K-pump activity (p less than 0.001) and an increase in Na,lithium(Li)-countertransport function (p less than 0.001) were observed. Na outward cotransport, Na leak, and K leak were not modified by the therapy. Direct correlation was found between the fall in mean blood pressure and in Na and K intraerythrocyte concentration (respectively, p less than 0.01 and p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of ketanserin on transmembrane sodium transport in erythrocytes. 168 23

Serotonin (5-HT) released from activated blood platelets plays a pivotal role in the development of thromboembolic complications. Essential hypertension, elevated plasma cholesterol, older age, and smoking are predisposing factors for these vascular events, and they all lead to platelet activation. In hypertensive patients, platelet 5-HT uptake is reduced with increasing age and blood pressure. This uptake inhibition is paralleled by an exaggerated platelet shape change and aggregation response. As a consequence, periplatelet 5-HT plasma concentrations are increased and promote further platelet aggregation and vasoconstriction. Low-density lipoproteins (LDL) induce a platelet shape change reaction and amplify the aggregatory response to serotonin. This effect is enhanced in smokers and even greater in hypertensive patients. LDL also inhibit endothelium-dependent relaxations to serotonin thereby unmasking the vasoconstrictor effect. 5-HT2-Receptor blockade with ketanserin interferes with this chain of events at several sites. Ketanserin inhibits platelet 5-HT release and 5-HT-induced platelet aggregation. It exerts a beneficial influence on the lipid profile. Blockade of 5-HT2 receptors leads to direct vascular smooth muscle dilatation as well as unopposed activation of endothelial 5-HT1-like receptors with the subsequent release of endothelium-derived relaxing factor. Taken together, the antihypertensive agent ketanserin may provide a new approach for multiple risk factor intervention therapy, eventually to prevent thromboembolic complications.
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PMID:Platelet serotonin-LDL interaction in essential hypertension. 171 71

The anti-hypertensive effect of ketanserin, a new antagonist of 5-HT2-serotonergic receptors, was evaluated in 10 patients with uncomplicated essential hypertension. At the end of 2 weeks of placebo wash-out and following 2 and 4 weeks of treatment with ketanserin (20 mg twice daily), blood pressure and heart rate were measured both in the supine and standing position. In addition, before and at the end of treatment, plasma renin activity (PRA), plasma concentration of aldosterone and the nocturnal urinary excretion of 6-keto-PGF1 alpha and TXB2, the two metabolites that largely reflect the renal synthesis of prostacyclin and thromboxane, respectively, were determined. The study was carried out in a metabolic ward where the intake of sodium was adjusted to 100-120 mmol day-1. Ketanserin significantly reduced blood pressure both in the supine and standing position with no significant change of heart rate. The treatment did not produce any variation of PRA, aldosterone, urinary excretion of 6-keto-PGF1 alpha or TXB2. These results indicate that ketanserin reduces blood pressure without interfering with the renin-angiotensin-aldosterone system or the renal synthesis of prostacyclin and thromboxane.
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PMID:Absence of effects of ketanserin on renal prostacyclin and thromboxane A2 in essential hypertension. 206 89

Ketanserin is a 5-HT2 receptor antagonist without partial agonist properties which also possesses weak alpha 1-adrenoceptor antagonistic activity, which may explain its antihypertensive mechanism of action in patients with essential hypertension. It also inhibits the effects of serotonin on platelets in cardiovascular disease, inhibits vasoconstriction caused by the amine, and when administered intravenously improves some haemorheological indices in patients with ischaemic diseases. The antihypertensive effect of oral ketanserin 40 mg twice daily is comparable with that of total daily doses of metoprolol 200 mg, propranolol 160 mg, captopril 100 mg, enalapril 20 mg, hydrochlorothiazide 50 mg, or alpha-methyldopa 1000 mg and is achieved without adverse effect on plasma lipoproteins or carbohydrate metabolism in patients with concomitant diabetes mellitus. Evidence from prospective studies suggests a greater antihypertensive efficacy in the elderly than in younger patients. In patients with intermittent claudication, results have been inconsistent in small studies, while a large study showed no improvement in pain-free walking distance but fewer amputations compared to placebo. In Raynaud's phenomenon symptomatic improvement relative to placebo was achieved in larger trials. Its role in preventing atherosclerotic complications requires further investigation. Ketanserin is reasonably well tolerated, the frequency of adverse effects being comparable with that of other antihypertensive drugs in controlled trials. Dizziness, tiredness, oedema, dry mouth and weight gain are the most commonly reported effects. Ketanserin prolongs QT interval in a dose-related manner, and when given in certain predisposing circumstances ventricular arrhythmias and syncope may occur. Administered intravenously, ketanserin 10mg followed by an infusion of 2 to 4 mg/h controls moderate to severe pre- and postoperative hypertension in most patients, acting as a balanced vasodilator, lowering cardiac pre- and afterload. Although the arrhythmogenic potential of ketanserin in patients receiving potassium-depleting diuretics requires suitable precautions, it appears that its antihypertensive activity is suited to the elderly provided plasma potassium concentrations are normal at the start of treatment and are maintained within the normal range.
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PMID:Ketanserin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in hypertension and peripheral vascular disease. 207 1

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, a serotonin antagonist, has recently been developed. This agent produces antihemagglutination and dilation of blood vessels. Blood pressure is also lowered by ketanserin. We investigated the effect of ketanserin on microhemodynamics and hemorheology in essential hypertension. Twenty patients with essential hypertension (8 males; 12 females; average age +/- SE-56.2 +/- 2.5 years). A single dose of 10 mg ketanserin was given orally to each patient, without breakfast, on the experiment day. Ketanserin treatment resulted in: redution in systolic and diastolic blood pressure; significant decrease in heart rate; increase in arteriole and venule internal diameters; increase in blood flow velocities and blood flow volumes; significant decreases in whole blood viscosities at high shear rate (94.5 sec-1) and at low shear rate (0.376 sec-1), with no change in plasma viscosities; significant shortening of plasma passage times; and marked decreases in blood concentrations of total protein, albumin, and globulin. These data suggest that ketanserin beneficially affects microhemodynamics and hemorheology.
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PMID:Effects of ketanserin on microhemodynamics and hemorheology in patients with essential hypertension. 228 38

Ten patients with essential hypertension and normal renal function were treated with ketanserin (20-40 mg twice a day), administered for 8 weeks. In all patients, the changes in systemic and renal hemodynamics, and in urine albumin excretion, were assessed. Ketanserin monotherapy effectively lowered blood pressure in all patients. No change in cardiac output, pulse rate and stroke volume was observed; peripheral vascular resistance was significantly decreased. Plasma volume was unaltered. Renal plasma flow, glomerular filtration rate and filtration fraction were stable, with a slight but not significant reduction in renal vascular resistance. Urine albumin excretion remained unchanged. No relevant side effects were observed during the treatment period. In conclusion, our results confirm that ketanserin alone is an effective antihypertensive agent in patients with uncomplicated essential hypertension. The blood pressure lowering effect is mainly due to the systemic vasodilatation; renal hemodynamics and function are well preserved.
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PMID:Antihypertensive therapy with ketanserin: effects on central and renal hemodynamics, and microalbuminuria. 230 49

Ketanserin (120 mg/day) or placebo was given orally to 14 patients with mild to moderate essential hypertension according to a double-blind crossover protocol, each treatment period lasting 6 weeks. Resting intraarterial pressure in the recumbent position was reduced from 150/84 to 141/77 mm Hg; the hypotensive effect persisted throughout an uninterrupted graded exercise test to the point of exhaustion. The hemodynamic effects were similar at rest and during exercise. Overall, systemic vascular resistance decreased by 14%, heart rate fell by 5%, but stroke volume and cardiac output increased. The pressor responses to methoxamine and to phenylephrine were reduced by ketanserin.
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PMID:Hemodynamic response to chronic ketanserin treatment in essential hypertension. 241 34

Ketanserin is a serotonin antagonist with high affinity for S2-serotonergic receptors, which mediate the vasoconstrictor effects of serotonin. It does not block the vasodilator effects of this monoamine, and it is devoid of agonist activity and serious central side effects. Ketanserin, however, also binds to alpha 1-adrenoceptors. The compound (10 mg i.v.) was given to 30 patients with essential hypertension and four normotensive patients with chronic autonomic failure, owing to an efferent sympathetic lesion. Ketanserin lowered systolic and diastolic arterial pressure by about 20%. The effects on cardiac output, cardiac filling pressures, forearm blood flow, renal blood flow, and glomerular filtration rate revealed a hemodynamic pattern compatible with dilatation of both resistance and capacitance vessels. These vasodilator effects were accompanied by moderate reflex stimulation of the heart. The drug did not alter the pressor effect of bolus injections of the alpha 1-adrenoceptor agonist phenylephrine, which contrasted with the competitive antagonism exerted by the alpha 1-adrenoceptor antagonist prazosin. Baroreflex-mediated bradycardia after phenylephrine also was not affected by ketanserin. The drug had a distinct hypotensive effect in patients with autonomic failure, despite the fact that these patients did not respond to the nonselective alpha-adrenoceptor antagonist phentolamine, 20 mg i.v. Thus, ketanserin is capable of lowering arterial pressure independently of alpha 1-adrenoceptor blockade. The results are therefore indirect evidence supporting a role of serotonin in hypertension.
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PMID:Ketanserin: a possible tool for studying the role of serotonin in hypertension. 241 35

Ketanserin is a serotonin (S2) blocker that reduces blood pressure (BP) in patients with essential hypertension preferentially by a reduction of peripheral vascular resistance. Heart rate is generally not affected or slightly reduced. When given in monotherapy on a 40 mg b.i.d. regimen, ketanserin reduces diastolic BP as effectively as metoprolol 100 mg b.i.d. or hydrochlorotiazide 25 mg b.i.d. The incidence of adverse reactions is low and comparable to these reference drugs. A satisfactory BP control is provided over a 24-h interval on a 40 mg b.i.d. dosage schedule, and the effect is maintained on a long-term basis, i.e., greater than 2 years. The response seems to be more marked in older patients, which may be due to an augmented platelet serotonin release and a vascular hypersensitivity in this age group. The future usefulness of ketanserin, as well as any other antihypertensive agent, will depend on its ability to prevent organ damage, as well as its ability to provide "quality of life" for the patient.
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PMID:A comparative and long-term evaluation of ketanserin in the treatment of essential hypertension. 241 38


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