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

Serotonin has complex effects on the cardiovascular system. In the intact animal it may cause increases or decreases of blood pressure and in isolated blood vessels contraction or relaxation depending on the species and vascular bed studied, the route of administration and the dosage used. Contractions evoked by the monoamine are mediated mainly by S2-serotonergic receptors on vascular smooth muscle; in addition, serotonin may act indirectly by amplifying the response to norepinephrine and other agonists, by displacing norepinephrine from adrenergic nerve terminals or releasing constrictor substance(s) from the endothelium. Dilatation in response to serotonin is mediated by endothelial and prejunctional S1-serotonergic receptors which pharmacologically resemble 5-HT1-binding sites. In hypertension, constrictor responses to serotonin are augmented, while the vasodilator effects of the monoamine are decreased. The constrictor response to serotonin is increased more than those to other agonists, suggesting a functional rather than a structural adaptation of the hypertensive blood vessel wall. In hypertension the turnover of circulating platelets, the major source of peripheral serotonin, is accelerated and the mechanisms for the removal of the monoamine are impaired. The functional changes of the blood vessel wall and platelets could play a role in the maintenance of the increased peripheral vascular resistance in chronic hypertension, and they could be involved in the pathogenesis of complications of the hypertensive process. The concept that serotonin plays a role in chronic hypertension is further supported by the antihypertensive properties of the S2-serotonergic antagonist, ketanserin.
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PMID:Serotonin and the blood vessel wall. 293 11

Serotonin induces constrictor responses on smooth muscle tissues from several vascular regions mainly by its interaction with serotonin-S2 receptor sites. The individual sensitivity of various blood vessels to serotonin may vary considerably. Serotonin (e.g. released from aggregating platelets) also induces vascular contractions by amplifying the response to other vasoactive substances. The vascular reactivity to serotonin can be markedly augmented by acute hypoxia (95% N2, 5% CO2; canine coronary arteries) and by cooling from 37 degrees to 29 degrees C (rabbit tibial and canine saphenous arteries). Blood vessels become hyperreactive to the vasoconstrictor component of serotonin in a number of disease states. Isolated perfused kidneys from spontaneously hypertensive rats (SHR) exhibit direct and indirect (amplifying) vasoconstrictor responses to serotonin. The amplifying effect of serotonin is significantly more pronounced in 6-month-old than in 2-month-old SHRs. Both the direct and indirect vasoconstrictor responses to serotonin, whether or not augmented by acute or chronic conditions, are inhibited by the serotonin-S2 receptor antagonist, ketanserin (4 X 10(-10) to 4 X 10(-7) mol/l). Both the hypersensitivity of vascular tissue to serotonin and the amplifying effect of the amine may greatly contribute to hypertension and other cardiovascular disorders.
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PMID:Augmentation of vasoconstrictor responses to serotonin by acute and chronic factors: inhibition by ketanserin. 293 13

Essential hypertension is a multifactorial disorder mediated by multiple mechanisms. Serotonin may cause vasoconstriction either directly or indirectly by amplifying the actions of vasoconstrictor substances. Clinical trials indicate that ketanserin, a serotonin antagonist, is effective in treating hypertension. It is desirable for an antihypertensive agent to enhance or preserve renal hemodynamic function. In this study, we evaluated the acute (1 week) and chronic (8 weeks) effects of ketanserin (20-40 mg twice a day) on glomerular filtration rate, renal plasma flow, and sodium excretion in patients with uncomplicated hypertension. Patients with untreated diastolic blood pressure (greater than 90 mm Hg) received either ketanserin or a placebo during an 8-week double-blind trial. Findings demonstrated that patients treated with ketanserin showed an increase in renal plasma flow compared with those who received placebo. Sodium excretion remained unchanged, indicating the absence of sodium retention during therapy. These results show that ketanserin lowers blood pressure in essential hypertension while preserving renal hemodynamics and function.
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PMID:Ketanserin in essential hypertension. Effects of blood pressure on renal hemodynamics. 304 33

1. In previous studies, exogenous serotonin (5-HT), administered intravenously, caused dose-related increases in mean arterial pressure and heart rate in conscious sheep. The 5-HT2 antagonist ketanserin (0.1 mg/kg per h, i.v.) was shown to lower blood pressure in the conscious sheep primarily through antagonism of alpha-adrenoceptors. 2. A newer 5-HT2 antagonist, ritanserin, is a more selective antagonist in vivo, as it attenuated or abolished pressor responses to exogenous 5-HT, but not to phenylephrine. 3. When infused alone, ritanserin (0.1 mg/kg per h, i.v.) failed to produce a decrease in blood pressure, suggesting that 5-HT antagonistic properties are not sufficient by themselves to lower blood pressure. 4. Ritanserin displayed a different metabolic profile to ketanserin, with a markedly decreased water intake. The mechanism of this effect is unresolved, but may imply a permissive role for 5-HT in the modulation of drinking responses in the sheep. 5. Ritanserin did not modify ACTH-induced hypertension in sheep.
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PMID:Ritanserin and serotonergic mechanisms in blood pressure and fluid regulation in sheep. 312 98

Intraplatelet serotonin (5-HT) content was determined in 23 patients with type I (insulin-dependent) diabetes mellitus (IDDM), 23 patients with type II (non-insulin-dependent) diabetes mellitus (NIDDM), 29 patients with peripheral vascular disease (PVD) and 34 age-matched normal subjects. Intraplatelet 5-HT content in normal subjects showed an age-related decline (r = -0.45; P less than 0.008), as has been previously demonstrated. The median 5-HT content in platelets of the young normal subjects was 4.36 (range: 3.62-6.79) nmol 10(-9) platelets, while that in the elderly normal subjects was 3.87 (range: 2.8-6.0) nmol 10(-9) platelets and that in young + elderly subjects was 4.05 (range: 2.8-6.8) nmol 10(-9) platelets. The median intraplatelet 5-HT content was significantly lower (P less than 0.002) in IDDM patients: 3.0 (range 1.3-6.3), NIDDM patients: 2.5 (range 1.7-5.8), PVD patients: 2.42 (range 0.94-4.98) nmol 10(-9) platelets than that in all young + elderly healthy subjects. The presence of hypertension in DM patients caused a small but significant (P less than 0.05) decrease in intraplatelet 5-HT content, whilst its presence had no effect in PVD patients. In a smaller study, it was established that NIDDM and PVD patients have significantly (P less than 0.002) greater plasma 5-HT concentrations than controls. Insulin-dependent diabetes mellitus patients had greater plasma 5-HT concentrations but this did not achieve statistical significance despite a 66% increment in its value.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intraplatelet serotonin in patients with diabetes mellitus and peripheral vascular disease. 313 26

The goal of this study was to determine whether responses of cerebral arterioles to products released by platelets are impaired in stroke-prone spontaneously hypertensive rats (SHRSP). The diameter of pial arterioles was measured during suffusion with adenosine 5'-diphosphate (ADP), serotonin, and the thromboxane analogue U-46619, using intravital microscopy in normotensive Wistar-Kyoto rats (WKY) and SHRSP (7-10 months old). Responses of cerebral arterioles to ADP and serotonin were profoundly impaired in SHRSP. ADP (10(-5) M) increased pial arteriolar diameter 17 +/- 3% (mean +/- SE) in WKY and only 4 +/- 1% in SHRSP. Serotonin (10(-5) M) increased pial arteriolar diameter 15 +/- 2% in WKY and, in contrast, reduced the diameter 13 +/- 1% in SHRSP. Nitroglycerin produced a similar dilatation of cerebral arterioles in WKY and SHRSP, suggesting that impairment of dilatation in SHRSP in response to ADP and serotonin was not related to nonspecific impairment of vasodilatation in SHRSP. The thromboxane analogue U-46619 produced a similar constriction of arterioles in WKY and SHRSP. We also examined the possibility that impaired dilator responses of cerebral arterioles in SHRSP in response to ADP and serotonin may be related to production of a cyclooxygenase vasoconstrictor substance. Indomethacin (10 mg/kg i.v.) partially restored dilator responses to ADP and serotonin in SHRSP, without altering responses in WKY. Thus, we speculate that vasoactive substances released by platelets may release a prostanoid constrictor substance from cerebral vessels of SHRSP and thereby predispose SHRSP to cerebral ischemia and, perhaps, stroke.
Hypertension 1988 Dec
PMID:Responses of cerebral arterioles to adenosine 5'-diphosphate, serotonin, and the thromboxane analogue U-46619 during chronic hypertension. 320 60

The role of serotonin in the pathogenesis of hypertension is not clear. Serotonin is produced by the enterochromaffin cells of the gut; the greater part of this is metabolised in the liver and lungs and nearly all of the remainder is taken up by the platelets. Consequently, circulating levels of serotonin are extremely low. The arterial wall possesses S2-serotonergic receptors, stimulation of which by serotonin leads to vasoconstriction. There are also serotonergic neurons in the central nervous system, particularly in the medulla, which are concerned with the neurogenic control of the circulation. Ketanserin has a high affinity for the S2-receptors, and thus it will antagonise the stimulating effect of serotonin at these receptors. It also has a weaker affinity for alpha 1-adrenoceptors and may act in part by antagonising the pressor effects of norepinephrine, either directly, or indirectly through a link between serotonin S2-receptors and alpha 1-receptors. Experimental evidence suggests that atheromatous lesions lead to increased sensitivity to the vasoconstricting effects of serotonin. This may be due in part to platelet adhesion to areas of endothelial damage, with an associated reduced presence of endothelial relaxing factor. In human hypertension, ketanserin appears to lower blood pressure more effectively in older patients, an effect which may be due to associated atheroma of the aorta and large arteries of these patients. Serotonin antagonism offers a novel approach to the treatment of the hypertensive patient. The increased effectiveness of ketanserin in elderly patients may be of particular importance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The relevance of serotonin antagonism in the treatment of hypertension. 324 Jul 30

The effect of ketanserin (0.15 mg/kg followed by an infusion at 6 mg/hr) was studied in 13 patients who developed hypertension (blood pressure greater than 150/90 mm Hg) after cardiopulmonary bypass (CPB) for coronary artery bypass grafting. Eleven patients responded to ketanserin with a decrease of arterial pressure from 159 +/- 15/83 +/- 10 mm Hg to 131 +/- 9/70 +/- 12 mm Hg (P less than 0.01), which was sustained during the subsequent infusion of ketanserin. Mean plasma ketanserin concentrations were maintained at 187 micrograms/L (range 118-525). No significant changes in plasma levels of 5-hydroxyindoles or in platelet 5-hydroxytryptamine content were observed during or after CPB, or after administration of ketanserin. Plasma epinephrine (398 +/- 124 pg/ml) and norepinephrine (1161 +/- 673 pg/ml) concentrations were markedly increased during the hypertensive period after CPB. Plasma epinephrine concentrations decreased (P less than 0.01) during ketanserin infusion to 213 +/- 101 pg/ml, whereas plasma norepinephrine concentrations did not change. The pressor response to three graded doses of phenylephrine was decreased during CPB (P less than 0.01), and a further decrease (P less than 0.05) occurred during infusion of ketanserin. The hypotensive effect of ketanserin after CPB may be attributable to alpha 1-adrenoceptor blockade rather than to its antiserotoninergic effect. Serotonin does not appear to be involved in the short-term disturbances of arterial pressure during or after CPB.
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PMID:Antihypertensive mechanism of ketanserin in postoperative hypertension after cardiopulmonary bypass. 327 83

Aggregating platelets release serotonin, which induces contraction of most vascular smooth muscle by activation of S2-serotoninergic receptors. Serotonin released in the circulation may contribute to the increase in peripheral resistance of hypertension as the responsiveness of blood vessels from hypertensive animals and humans to the vasoconstrictor action of the monoamine is augmented. The data obtained with the new antihypertensive agent ketanserin may favor that interpretation. Ketanserin is a selective S2-serotoninergic antagonist with additional alpha 1-adrenergic blocking properties. In humans, it has a terminal half-life of 12 to 25 hours and is eliminated predominantly by the liver. The hemodynamic profile of ketanserin is that of a vasodilator drug with actions on both resistance and capacitance vessels. On short-term intravenous administration, it lowers blood pressure in hypertensive patients with minimal reflex changes in cardiovascular function. When given orally long term to hypertensive patients, ketanserin causes a sustained reduction in arterial blood pressure, comparable to that obtained with either beta-adrenergic blockers or diuretics. Several studies have shown a greater efficacy in older (greater than 60 years of age) than in younger patients independent of starting pressure. Side effects mainly consist of dizziness, somnolence, and dry mouth, but they are usually not severe. The mechanism underlying the antihypertensive effect of ketanserin is unclear. It cannot be attributed to either S2-serotoninergic or alpha 1-adrenergic blockade alone, but an interaction between the two effects appears to be required.
Hypertension 1988 Feb
PMID:Serotoninergic mechanisms in hypertension. Focus on the effects of ketanserin. 327 10

Serotonin has various hemodynamic effects, and may play a role in systemic hypertension. Ketanserin is a specific S2 serotonergic receptor blocker with possible adrenergic blocking activities that has clinical utility in the treatment of hypertension. The drug may have particular advantages for various patient populations.
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PMID:Serotonin antagonism in the treatment of systemic hypertension: the role of ketanserin. 327 88


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