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

When the local concentration of serotonin is raised during platelet aggregation, the direct effect of serotonin on vascular smooth muscle is to activate the contractile process. Serotonin also amplifies the constrictor responses to other neurohumoral mediators. Vascular smooth muscle can become hyperreactive to the vasoconstrictor effects of serotonin both acutely (e.g., local cold, hypoxia) and chronically (e.g., atherosclerosis, hypertension). Vasodilator responses to serotonin can be unmasked by blockade of its vasoconstrictor component. The inhibition by ketanserin of the various vasoconstrictor and platelet-aggregating effects of serotonin presumably contributes to the therapeutic effects of the compound.
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PMID:Serotonin and the blood vessel wall. 241 58

Serotonin levels and turnover were analyzed in discrete forebrain and mesencephalic nuclei of young (4-week-old) and adult (14-week-old) spontaneously hypertensive rats and age-matched normotensive control Wistar Kyoto rats. Most changes observed were age-dependent, and occurred only in young, early hypertensive rats. Both serotonin levels and the accumulation rate of 5-hydroxy-tryptophan after L-amino acid decarboxylase inhibition were higher in the nuclei periventricularis and paraventricularis of the hypothalamus of young hypertensive rats than in controls. In addition, 4-week-old spontaneously hypertensive rats showed higher 5-hydroxytryptophan accumulation rates in the nuclei supraopticus and dorsomedialis of the hypothalamus than controls. The only difference in serotonin metabolism found in adult hypertensive rats was high serotonin concentration in the median eminence of the hypertensive animals. Our results suggest the presence of anatomically specific, age-dependent alterations in serotonin metabolism, localized to selected hypothalamic nuclei in young hypertensive rats. These data support a role for the hypothalamic serotonin in the development of the spontaneous (genetic) hypertension in the rat.
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PMID:Serotonin turnover in discrete hypothalamic nuclei and mesencephalic raphe nuclei of young and adult spontaneously hypertensive rats. 242 65

Our previous studies have demonstrated that the specific dopamine D2 receptor agonist, quinpirole (LY171555), has a pressor effect in conscious normotensive rats and that this is accompanied by a centrally mediated increase in sympathetic activity and arginine vasopressin release. This pressor response to quinpirole is blunted in the DOCA/NaCl hypertensive rat. To examine the hypothesis that the responsiveness of the central noradrenergic and serotonergic systems to quinpirole treatment is altered in DOCA/NaCl rats, the norepinephrine (NE), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) contents of hypothalamic and brainstem areas were measured in 4-week DOCA/NaCl hypertensive and H2O control rats 15 minutes after the intravenous administration of quinpirole (1 mg/kg). The results demonstrate that quinpirole selectively reduced (26%) posterior hypothalamic NE content in control rats, but not in DOCA/NaCl hypertensive rats. The NE content in the spinal cord and 5-HIAA content in the pons were greater in DOCA/NaCl rats than in normotensive controls in both saline and quinpirole treated groups. Our data suggest that the specific D2 agonist may effect its central pressor response by stimulating NE release from posterior hypothalamic area, a "pressor" region of hypothalamus, and that this D2 agonist induced pressor mechanism may be blunted in DOCA/NaCl hypertension.
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PMID:Blunted responsiveness of posterior hypothalamic norepinephrine to quinpirole in DOCA/NaCl hypertensive rats. 244 May 28

Serotonin (5-hydroxytryptamine; also called 5-HT) modifies cardiovascular activity by central as well as peripheral sites of action. When 5-HT is injected within the central nervous system, depending upon the dose and site of administration, either a pressor or a depressor effect is observed. Recent findings suggest that this depressor effect may be mediated by central "5-HT1-like" receptors, since certain compounds that exhibit a high affinity for the 5-HT1A binding site can reduce blood pressure by a central action in both hypertensive and normotensive animals. Peripherally, 5-HT elicits vasodilatation (both directly and indirectly via presynaptic sympathoinhibition and release of vasodilator substances from endothelium) or vasoconstriction (with associated amplification of noradrenaline response) of mainly "large" conductance arteries mediated by, respectively, "5-HT1-like" and 5-HT2 receptors. Of the various antagonists at 5-HT receptors, it is only ketanserin that effectively lowers arterial blood pressure. However, since it is unlikely that the very low concentrations of 5-HT in plasma exert a significant influence on the maintenance of peripheral vascular resistance, the blockade of 5-HT2 receptors by ketanserin does not seem to explain the reduction of blood pressure in hypertension. Indeed, apart from the undoubtedly potent 5-HT2 receptor blockade, ketanserin also has alpha 1-adrenoceptor antagonist, central vasomotor depressant, and "direct" vasodilator properties, which can explain its antihypertensive action.
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PMID:Serotonin agonists and antagonists in experimental hypertension. 244 59

The present article deals with the pathophysiological role of serotonin in cardiovascular disease and in other disorders that are accompanied by cardiovascular pathophysiological events. The distribution of serotonin over various organs and tissues and the presence of several types of 5-HT receptors would suggest a rather important physiological role of serotonin. However, a modest serotonergic role could only be shown for the microcirculation and for the regional circulation of the brain and the intestinal wall. An important pathological role of serotonin in the carcinoid syndrome, in migraine, and in peripheral vascular disease is beyond debate, although many details remain to be established. The possibility that serotonergic mechanisms contribute to Raynaud's phenomenon and other vasospastic disorders is the subject of present discussions, although firm evidence for this view is not widely available. An involvement of peripheral serotonin in the genesis and maintenance of essential hypertension seems very unlikely, although vascular damage due to hypertension is probably enhanced by serotonin released from aggregating platelets. This ancillary process is, in particular, to be anticipated in older patients, with vascular walls predamaged by atherosclerosis. For this reason, pharmacological blockade of 5-HT2 receptors may be of potential therapeutic benefit in this category of patient. Finally, the involvement of central serotonergic mechanisms in hypertensive disease cannot be ruled out.
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PMID:Pathophysiological relevance of serotonin. 244 63

In spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats it was examined whether the effects mediated by presynaptic 5-HT1 receptors on noradrenergic and serotoninergic neurons are altered in hypertension. Vascular strips (arteria iliaca, vena cava) as well as brain slices (nucleus tractus solitarii, hypothalamus, cortex) were prepared from 5-7-, 9-11-, and 19-22-week-old SHR and WKY rats (mean systolic blood pressure: 111, 183, and 212 and 105, 113, and 106 mm Hg, respectively). Subsequent to incubation with [3H]noradrenaline ([3H]NA; vascular strips) and [3H]serotonin ([3H]5-HT; brain slices), the tissues were superfused and the effects of 5-HT on the electrically evoked [3H]monoamine overflow were studied. The inhibitory effect of 5-HT on the evoked [3H]NA release in the arterial strips did not differ between both strains (at any age). In strips of the vena cava, the maximum inhibitory effect of 5-HT on evoked release was, at any age, more pronounced in SHR than in WKY rats. In slices of the three brain regions, the evoked [3H]5-HT release was similar in SHR and WKY rats. Likewise, the inhibitory effect of 5-HT on the evoked release did not differ in both strains at any age. The present results indicate that the inhibitory effect mediated by presynaptic 5-HT1 receptors is more pronounced in the vein, but is identical in the artery, of SHR rats compared to WKY rats. 5-HT release in the brain and its modulation via inhibitory presynaptic 5-HT1 autoreceptors do not differ in both strains.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Presynaptic serotonin receptors on peripheral noradrenergic and central serotoninergic neurons of spontaneously hypertensive and Wistar-Kyoto rats. 244 71

Rat brain tissues preincubated with [3H]serotonin ([3H]5-HT) or [3H]norepinephrine ([3H]NE) were superfused in the presence of an inhibitor of serotonin or NE uptake, respectively. The electrically (3 Hz) evoked [3H]5-HT release from slices of the medulla oblongata [containing the nucleus tractus solitarii (NTS)] from Wistar rats was inhibited by 5-HT and NE, and these effects were counteracted by metitepine and phentolamine, respectively. The evoked [3H]5-HT release in slices from the cortex, medulla oblongata, and hypothalamus of 5-7-, 9-11-, and 19-22-week-old spontaneously hypertensive rats (SHR) did not differ from that in slices from age-matched Wistar-Kyoto rats (WKY). Nor was there any difference between strains for: the inhibitory effects of 5-HT and NE and the facilitatory effect of metitepine on the evoked [3H]5-HT release; the shift to the right of the concentration-response curves of 5-HT and NE by metitepine and phentolamine, respectively; the potassium (12 mM)-evoked [3H]5-HT release from cortex synaptosomes and its inhibition by 5-HT; the electrically evoked [3H]NE release in cortex slices, its inhibition by NE, and the shift to the right of the concentration-response curve of NE by phentolamine. The results provide evidence that 5-HT release in the rat brain NTS can be inhibited by 5-HT receptors and alpha-adrenoceptors. 5-HT release and its modulation by presynaptic 5-HT1 receptors and alpha 2-adrenoceptors as well as NE release and its modulation by presynaptic alpha 2-adrenoceptors do not differ between SHR and WKY rats. It may be of therapeutic relevance that according to these results the effects of 5-HT1 receptor agonists activating presynaptic 5-HT autoreceptors are not attenuated in this type of hypertension. It has been suggested that such agonists can be developed as a new class of antihypertensive drugs.
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PMID:Presynaptic serotonin receptors and alpha-adrenoceptors on central serotoninergic and noradrenergic neurons of normotensive and spontaneously hypertensive rats. 245 37

Serotonin enhances (amplifies) the vasoconstrictor effect of norepinephrine not only on isolated large blood vessels and isolated perfused vascular beds but also in vivo. This amplification can be observed with endogenous serotonin released from aggregating platelets and with endogenous norepinephrine released from the adrenergic nerves in the blood vessel wall. It is due to an interaction between S2-serotonergic and alpha 1-adrenergic mechanisms. Combined S2-serotonergic and alpha 1-adrenergic antagonism is more effective than either one alone against contractions evoked with the combination of serotonin and an alpha 1-adrenergic agonist. In spontaneously hypertensive rats, S2-serotonergic antagonism alone does not reduce blood pressure but combined S2-serotonergic and alpha 1-adrenergic blockade lowers blood pressure more than alpha 1-adrenergic blockade alone. This suggests that the interaction between S2-serotonergic and alpha 1-adrenergic vasoconstrictor responses may play a role in the maintenance of high blood pressure.
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PMID:Interaction between S2-serotonergic and alpha 1-adrenergic receptor activities at vascular sites. 245 6

Serotonin metabolism was investigated in 15 patients (8 women, 7 men) with decreased renal function (clearance of endogenous creatinine = 0.07-0.74 ml/s) and compared to the values obtained in healthy controls. In spite of thrombocytopenia, the patients' platelet serotonin concentrations (1.99-47.6 nmol/10(9) platelets) as well as the plasma serotonin levels (190-2,176 nmol/l) were significantly higher than in controls (1.36-7.87 nmol/10(9) platelets, p less than 0.05; 0-500 nmol/l, p less than 0.001). The low urinary serotonin output (0-414 to 167-1,187 nmol/24 h in controls, p less than 0.001) probably reflects its decreased synthesis in the residual renal parenchyma. 5-Hydroxyindolacetic acid was excreted in normal amounts. The impairment in serotonin metabolism is closely correlated with the decrease in renal function. The data document accumulation of serotonin in the circulation. This impairment could contribute to platelet hyperaggregation and/or consumptive hypocoagulation, maintenance of hypertension, and acceleration of atherosclerosis.
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PMID:Serotonin metabolism in patients with decreased renal function. 247 19

The role of serotonin (5-HT) in blood pressure (BP) regulation was reviewed. Central and peripheral 5-HT receptors can be divided into three receptor subtypes: 5-HT1 (5-HT1A, 5-HT1B, 5-HT1C), 5-HT2 and 5-HT3 receptors. The selective agonists and antagonists of these receptor subtypes are useful for investigating the BP regulation by 5-HT. The central 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) produced hypotension and decreases in sympathetic nerve activity (SNA). This suggests that central 5-HT may cause decreases in both BP and SNA via 5-HT1A receptors. Since the 5-HT2 receptor antagonist ketanserin, which has an antihypertensive effect, decreased SNA and the 5-HT2 agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) increased SNA, central 5-HT2 receptors may be connected with the 5-HT-induced increases in both BP and SNA. On the other hand, ketanserin's antihypertensive effects via its 5-HT2 receptor blocking action in the vascular system indicates that peripheral 5-HT may contribute to the initiation or the maintenance of elevated vascular resistance in several forms of hypertension including essential hypertension. However, ketanserin also possesses alpha 1-adrenoceptor blocking action, and its precise antihypertensive mechanism has not been established. Further study of the antihypertensive mechanism of ketanserin will help clarify the precise role of 5-HT in BP regulation.
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PMID:[Serotonin and blood pressure regulation--antihypertensive mechanism of ketanserin]. 257 64


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