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

In an open, clinical trial comprising a total of 49 depressed in-patients, a new selective 5-HT uptake inhibitor citalopram was administered by intravenous infusion in doses of 20-60 mg once daily for per 3 weeks. The therapeutic effect was assessed globally and by means of the CPRS subscale for depression (MADRS). About 40 per cent of the patients showed a complete response whereas about 25 per cent showed a partial response. Side effects which were rated globally and recorded according to a check-list were generally mild and infrequent. The side-effects most frequently observed were tremor, drowsiness, and dizziness which occurred in about 15 per cent of the patients.' Three patients were withdrawn prematurely because of nausea and one because of a skin rash. Cardiovascular recordings were normal except for one patient, who developed a hypertension which may have been related to the test drug. No pathological laboratory values were detected during the trial period. The authors conclude that intravenously administered citalopram is well suited for the treatment of depressed patients.
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PMID:[Citalopram. An open study of a highly selective serotonin-uptake inhibitor administered by infusion to depressive patients]. 331 9

Quipazine, a nonselective serotonin (5-HT) agonist, has been shown to increase plasma renin activity (PRA). The present study examined the effects of quipazine on mean arterial pressure (MAP), heart rate (HR) and PRA in conscious, chronically catheterized male rats. Quipazine caused dose (0.3-3.0 mg/kg i.v.)-and time (up to 30 min)-dependent increases in MAP and PRA. The maximum increases in MAP (control = 94 +/- 2 mm Hg, 3 mg/kg = 155 +/- 1 mm Hg) and PRA (nanograms of angiotensin 1 per milliliter per hour; control = 2.5 +/- 0.2, 3 mg/kg = 25.2 +/- 5.9) were observed 5 min after quipazine. HR tended to decrease, but a significant bradycardia was observed only 15 min after 3 mg/kg. The selective 5-HT2 antagonist LY 53857 (1 mg/kg i.v.) did not affect MAP, HR or PRA per se, but at 0.03 to 1.0 mg/kg totally abolished the pressor response to quipazine (3 mg/kg). At 0.01 mg/kg, LY 53857 attenuated quipazine-induced hypertension, whereas 0.003 mg/kg was ineffective. Total blockade of quipazine-induced renin secretion was produced by LY 53857 at 0.003 mg/kg, and the response was still reduced by 50% at 0.001 mg/kg. In summary, although quipazine increases arterial pressure and renin secretion, endogenous 5-HT does not tonically control MAP or PRA in conscious, unrestrained, normotensive rats through 5-HT2 receptors. The 10-fold difference in the dose of LY 53857 necessary to block the pressor and renin responses may be due to subtle differences in receptor subtypes, or to pharmacokinetic properties favoring antagonism of quipazine-induced renin secretion.
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PMID:Activation of serotonin2 (5-HT2) receptors by quipazine increases arterial pressure and renin secretion in conscious rats. 332 Mar 45

In view of its vasoconstricting action and of its stimulating effect on aldosterone biosynthesis, serotonin (5-hydroxytryptamine, 5-HT) could play a role in the genesis and/or maintenance of hypertension. The effects are mediated by different specific receptors whose transmembrane signaling system is not elucidated. We have used the fluorescent probe quin 2 to study the effect of 5-HT on cytosolic free calcium in enzymatically dispersed bovine adrenal glomerulosa cells and in cultured rat aortic smooth muscle cells. We also examined the effect of 5-HT on prostacyclin production by rat aortic smooth muscle cells. Serotonin did not modify the level of cytosolic free calcium in adrenal glomerulosa cells. In contrast, serotonin induced rapid, concentration-dependent (10(-8) -10(-5) M) rises of cytosolic free calcium in monolayers of cultured rat aortic smooth muscle cells, from a basal level of 153 +/- 27 nM to peak levels of about 400 nM. Ketanserin (10(-6) M), a specific 5-HT2-receptor antagonist completely blocked the free calcium rise induced by 5-HT. 5-HT induced a concentration-dependent increase in 6-keto-PGF1 alpha production in smooth muscle cells, which was suppressed by ketanserin, indomethacin or removal of calcium from the incubation medium. In contrast nifedipine (10(-6) M) did not modify the response to 5-HT while it abolished the response to vasopressin and did not modify the response to angiotensin II. We conclude that the 5-HT receptors of adrenal glomerulosa cells and vascular smooth muscle cells are linked to two distinct signalling systems which mediate the different biological responses.
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PMID:Effect of serotonin on cytosolic free calcium in adrenal glomerulosa and vascular smooth muscle cells. 332 95

In the present study we examined the effect of depletion of central nervous system serotonin by 5,7-dihydroxytryptamine on blood pressure in male Wistar rats. We also analyzed the relationship between the serotonergic and renin-angiotensin systems. Blood pressure was determined before and after intracisternal administration of 5,7-dihydroxytryptamine, 200 micrograms in saline with 1 mg/ml ascorbic acid (n = 9). Control rats (n = 8) received intracisternal vehicle. Before sacrifice, blood and cerebrospinal fluid samples were obtained. The brain was dissected in several areas. Serotonin, norepinephrine, angiotensinogen, and reninlike concentrations were determined in the brain parenchyma; angiotensinogen concentration was evaluated in cerebrospinal fluid and plasma samples; plasma renin activity was also measured. Treatment produced a significant decrease in blood pressure (-10 mm Hg; p less than 0.025) and, simultaneously, a high depletion of serotonin stores in the studied central areas (p less than 0.001), except in the cerebral cortex. Reninlike concentration was increased in the medulla oblongata (p less than 0.005) and the brainstem (p less than 0.02) after 5,7-dihydroxytryptamine treatment. Angiotensinogen concentration was decreased in the hypothalamus and elevated in the spinal cord. Angiotensinogen concentration in cerebrospinal fluid, plasma angiotensinogen concentration, and plasma renin activity did not change with treatment. Serotonin concentration in the cerebrospinal fluid remained unchanged, while the 5-hydroxyindoleacetic acid level was diminished (-47%; p less than 0.001). Intracisternal administration of 5,7-dihydroxytryptamine produced a hypotensive effect in normal rats and several modifications of the renin-angiotensin complex, suggesting a relationship between the monoaminergic and peptidergic systems.
Hypertension 1988 Feb
PMID:Effect of central serotonin depletion on blood pressure and the renin system in rats. 334 56

Serotonin content and accumulation in platelets and its release from them, as well as changes in thrombus formation in mesenteric arterioles and venules of the small intestine have been investigated in control rats and rats with spontaneous hypertension (SHR). Serotonin accumulation in platelets was determined upon its incubation with platelets. Disodium ADP salt was used as an inductor of release. Laser-induced thrombosis was caused by microvessels exposure to impulse laser irradiation. The control animals revealed a significant difference between the initial serotonin platelet level and serotonin level upon incubation and release; in values, the values of basic thrombus-forming parameters were higher than in arterioles. In SHR there is a decrease in biogenic amine content in platelets, a depression in its accumulation and release, an increase in the time of thrombus growth, its size up to the separation of the first embolus and its length along the vascular wall. It is concluded that spontaneous hypertension is characterized by decreased functional activity of platelets and depressed resistance of arterioles and venules to thrombus formation.
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PMID:[Serotonin metabolism in thrombocytes and microvascular hemostasis in spontaneous arterial hypertension]. 334 66

The present study investigated the metabolism of serotonin (5-HT) in rats made hypertensive by treatment with DOCA/NaCl. 5-Hydroxytryptamine and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA) were significantly elevated in a number of regions of the brain in rats treated for 2 weeks with DOCA/NaCl. Elevations in levels of 5-HIAA were present with 4 weeks of treatment with DOCA/NaCl but levels of 5-HT were not altered. No changes in the metabolism of 5-HT were detectable with 5 weeks of treatment with DOCA/NaCl. Levels of tryptophan were also elevated in a number of regions of the brain by treatment with DOCA/NaCl. Alterations in norepinephrine (NE) in the brainstem were present with 2, 4 or 5 weeks of treatment with DOCA/NaCl. The neurochemical effects of muscimol, a GABA agonist, were also investigated in rats treated with DOCA/NaCl for 4 weeks. Significant increases in levels of 5-HIAA and 5-HT were present in rats treated with DOCA/NaCl but not in controls, 15 min after intraventricular administration of muscimol (1.0 microgram/300 g body weight). Sixty min after muscimol, 5-HIAA was increased in both rats treated with DOCA/NaCl and control rats, but 5-HT was only increased in the hypothalamus. Treatment with DOCA/NaCl produced changes in the metabolism of 5-HT that may be important in the genesis of hypertension, but are not required for the maintenance of elevated arterial pressure. A disturbance of GABA-5-HT interactions between GABA and 5-HT in brainstem sites may also contribute to the pathogenesis of hypertension induced by DOCA/NaCl.
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PMID:Central serotonergic alterations in deoxycorticosterone acetate/NaCl (DOCA/NaCl)-induced hypertension. 341 40

Serotonin may cause vasodilatation or vasoconstriction. In hypertension the vasoconstrictor effects of serotonin predominate. Experiments were designed to study the effects of serotonin on coronary flow in isolated hearts of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. The hearts were paced at constant rate and perfused by the Langendorff technique at constant pressure (75 cmH2O). In WKY rats serotonin (10-9 to 10-5 mol/l) caused concentration-dependent increases in coronary flow and a decrease in cardiac performance. In SHR, the monoamine caused concentration-dependent, partially reversible decreases in coronary flow, and a marked decrease in cardiac performance. The inhibitor of cyclo-oxygenase indomethacin prevented the decrease in coronary flow and cardiac performance caused by serotonin in SHR, but did not affect the increase in coronary flow in WKY rats. These experiments suggest that in the coronary circulation of SHR the response to serotonin is shifted from vasodilatation to vasoconstriction. The mediator of this vasoconstriction is probably a product of cyclo-oxygenase.
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PMID:Serotonin reduces coronary flow in the isolated heart of the spontaneously hypertensive rat. 347 97

Serotonin released from aggregating platelets can reach sufficient concentrations to affect local vascular function in a number of ways. The monoamine can cause contraction of blood vessels by its direct action on smooth muscle or by potentiating the effect of other vasoconstrictor agents. It can also induce vasodilatation by a direct relaxing effect on smooth muscle, by inhibition of adrenergic nerves, and by release of an uncharacterized relaxing factor from endothelial cells. One of its most likely physiological roles is to aid in haemostasis by promoting platelet aggregation and by causing local vasoconstriction at sites of injury. It probably has a role in some forms of vascular pathology as well: it may contribute to vasospasm of cerebral, coronary, and digital arteries, particularly if there is endothelial dysfunction or damage. Much evidence has implicated serotonin (5-hydroxytryptamine) in the pathogenesis of migraine. Serotonergic agonists, such as ergotamine, and antagonists, such as methysergide and pizotifen, are both used in therapy of migraine. Promising but conflicting early results have not yet defined a place for serotonergic antagonists in other vasospastic disorders. The antihypertensive efficacy of one serotonergic antagonist, ketanserin, raises questions about the possible involvement of serotonin in either the initiation or the maintenance of the elevated peripheral vascular resistance in several forms of hypertension, including essential hypertension.
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PMID:Serotonin and the vascular system. Role in health and disease, and implications for therapy. 351 33

Serotonin induced a transient elevation in the levels of cytosolic calcium in cultured rat vascular smooth muscle cells. Ketanserin, a selective antagonist of serotonin 2 receptors, dose-dependently inhibited the elevation of cytosolic calcium induced by serotonin, and ultimately unmasked a serotonin-induced decrease in the levels of cytosolic calcium. These observations show that serotonin has direct and dual effects, that is, it increases and decreases cytosolic free calcium concentrations in vascular smooth muscle cells, in culture. Knowledge of such events is important because serotonergic inhibitors may prove to be useful drugs for treating clinical hypertension and vasospastic disorders.
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PMID:Serotonin-induced cytosolic free calcium transients in cultured vascular smooth muscle cells. 356 35

Platelet serotonin (5-HT) content was investigated in 35 essential hypertensive patients and in 58 normotensive subjects. A significant decrease of platelet 5-HT content was observed in both hypertensive men and women in respect to normotensive controls. This decreased platelet 5-HT content appears to be linked to a reduced capacity of platelets to take up 5-HT. Maximal velocity of 5-HT uptake was shown to be reduced in platelets from hypertensive patients and significantly correlated to platelet 5-HT content. No concomitant change of uptake Michaelis constant (KM) was observed. The great sensitivity of human platelets to very low concentrations of ouabain was demonstrated when incubation times were prolonged. The decreased Vmax observed in platelets from hypertensive patients and reproduced by ouabain inhibition could conceivably be linked to the presence of a circulating ouabain-like factor in hypertension.
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PMID:Reduced serotonin content and uptake in platelets from patients with essential hypertension: is a ouabain-like factor involved? 357 17


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