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

Recently, the serotonergic nervous system has been receiving attention, as it participates in the hemodynamic regulation as well as in the pathogenesis of hypertension. The purpose of this experiment is to investigate the role of the central and peripheral serotonergic receptor in the hemodynamic responses induced by intracerebroventricular (i.c.v) administration of 5-hydroxytryptamine (5-HT). Eight week-old male spontaneously hypertensive rats (SHR) and age matched Wistar Kyoto rats (WKY) were used, and the experiment was performed under conscious and minimum restrained states. Five micrograms of 5-HT was given i.c.v. followed by i.c.v. administration of 200 micrograms ketanserin. Mean arterial pressure (MAP) and heart rate (HR) were observed continuously for 30 minutes. Then 5 micrograms of 5-HT was given i.c.v. again in the same rat (SHR -IC group, n = 7; WKY-IC group, n = 7). The rest of the rats received 200 micrograms of ketanserin intravenously (i.v.) after i.c.v. administration of 5 micrograms 5-HT, and the same amount of 5-HT was given i.c.v. after the ketanserin i.v. (SHR-IV group, n = 7; WKY-IV group, n = 6). Five-HT elicited a significant pressor response in all groups of rats and a slight non-significant increase in HR. In SHR-IC group and WKY-IC group, neither ketanserin i.c.v. nor the second 5-HT i.c.v. administration caused significant changes in MAP and HR. In SHR -IV group, i.v. ketanserin caused a significant decrease in MAP (-8.8 +/- 1.4 mmHg), but no significant change in MAP in WKY-IV group (-1.1 +/- 1.2 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The effects of ketanserin on the hemodynamic response after intracerebroventricular administration of 5-hydroxytryptamine]. 380 31

The 5-hydroxytryptamine (5HT)-system of human blood platelets consists of a relatively specific uptake mechanism for 5HT at the plasma membrane, intracellular storage organelles (dense bodies), a metabolizing enzyme (monoaminoxidase B) and a 5HT2-receptor whose stimulation leads to activation of the phosphatidylinositide turnover, a rise in free cytoplasmic Ca2+, phosphorylation of proteins and a shape change reaction. There is neither a relevant 5HT-biosynthesis nor a marked physiological 5HT-turnover in platelets. Under physiological conditions the platelet 5HT-system may have a role as a scavenger for free extracellular 5HT and in hemostasis. Disturbances which have been described in pathophysiological states include impairment of 5HT-uptake (hypertension, migraine), impairment of 5HT-storage (storage pool deficiencies, thromboembolic disorders, hypertension) and increased sensitivity to activating agents like 5HT (cardiovascular disorders, diabetes). Besides their role in physiology and pathophysiology platelets may be useful partial models for vascular smooth muscle cells.
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PMID:The 5-hydroxytryptamine system of blood platelets: physiology and pathophysiology. 381 34

Intrinsic vascular responsiveness was examined in isolated, helically cut strips of cystic artery from 32 normotensive women. Contractions were elicited by vasopressin, norepinephrine, 5-hydroxytryptamine and transmural electrical stimulation. Of the 32 subjects, 17 had a family history of hypertension in a first-degree relative (parent, sibling, or adult offspring) and 15 had no family history of hypertension. The ages and mean arterial blood pressures of the two groups were not different: 39 +/- 12 versus 35 +/- 11 years (mean +/- SD; p = 0.263) and 87 +/- 4 versus 85 +/- 5 mm Hg (p = 0.214) respectively. The vasopressin dose-response curve was significantly shifted to the left for arteries of those subjects with a family history of hypertension compared with that for arteries of subjects with no family history (e.g., response--percent of norepinephrine maximum--to 100 mU/ml = 31 +/- 23 versus 12 +/- 16; p = 0.014). All other responses were not significantly different, although in general the arteries of those subjects with a family history tended to have greater responses to all stimuli except norepinephrine. Arteries from the two groups did not differ with respect to physical dimensions (e.g., cross-sectional area), passive mechanical properties, or maximal responses to norepinephrine. The data indicate that altered intrinsic vascular responsiveness is linked to a family history of hypertension in normotensive subjects and thus could play a role in the familial aggregation of elevated blood pressure.
Hypertension
PMID:In vitro arterial responses to vasopressin in subjects with a family history of hypertension. 398 67

1. Acute systemic anaphylaxis in calves was characterized by marked systemic hypotension; hypertension in the pulmonary arteries and abdominal vena cava, and transient apnoea. Calves responded with a second reaction to antigen, but a third anaphylactic response could not be evoked.2. Suppression of systemic anaphylaxis could not be effected with mepyramine, whereas methysergide or diethylcarbamazine each suppressed anaphylaxis by 50%. Disodium cromoglycate alone did not inhibit anaphylaxis: however, when disodium cromoglycate was combined with diethylcarbamazine almost total suppression (85%) was achieved. Sodium meclofenamate also was a powerful inhibitor of anaphylaxis (80%). It is tentatively suggested that slow reacting substance (SRS-A) may be an important mediator of bovine anaphylaxis.3. Bilateral vagotomy did not modify the circulatory responses to injected histamine, 5-hydroxytryptamine (5-HT) or antigen, whereas the effects of these agents on ventilation (apnoea) were abolished by vagotomy.4. Plasma histamine concentration was increased during anaphylaxis, whereas plasma 5-HT was not. Whole blood histamine concentration fell sharply and remained depressed during 20 min of anaphylactic shock. Reduced whole blood histamine levels probably reflect the severe leucopoenia in the calves.5. Histamine concentrations in six tissues taken from calves subjected to anaphylaxis were not different from those in control calves; mast cells were of similar numbers to controls, but showed some swelling, granular spilling and metachromasia.6. Histamine, 5-HT, bradykinin and antigen caused increased pulmonary artery perfusion pressure and ventilation resistance in isolated lungs from sensitized calves. However, there was no difference in histamine and 5-HT concentration in perfusates obtained during antigen infusion of sensitized and control lungs.7. Systemic anaphylaxis of calves may result from the interaction of histamine, 5-HT and SRS-A. The present data implicate (by indirect measurement) SRS-A as an important mediator of anaphylaxis in this species.
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PMID:Acute systemic anaphylaxis in the calf. 414 91

1. The effects of bradykinin (1-5 mug) injected into the cannulated lateral cerebral ventricles were studied in unanaesthetized rabbits before and after intravenous atropine, diphemanil and morphine.2. The intraventricular injections of bradykinin produced a short-lasting phase of behavioural excitation with vocalization followed by sedation. The behavioural excitation was associated with desynchronization in the electrocorticogram (e.co.g.), bradycardia and hypotension followed by tachycardia and hypertension. Tachypnoea was also observed. The subsequent phase of sedation was more prolonged and associated with synchronization of the e.co.g. and signs of catalepsy. Intense miosis was present during both phases.3. With repeated intraventricular injections of bradykinin, excitation, miosis, cardiovascular responses and tachypnoea diminished and eventually disappeared but the sedation did not exhibit tachyphylaxis.4. Atropine abolished the e.co.g. desynchronization, vocalization and bradycardia, reduced the duration of the excitatory and sedatory phase, diminished the tachycardia and hypotension, enhanced the hypertension, but did not affect the miosis and tachypnoea.5. Diphemanil affected only the cardiovascular effects produced by intraventricular bradykinin. They were affected in the same way as by atropine.6. Morphine did not affect the excitatory phase, but enhanced the cardiovascular effects produced by intraventricular bradykinin.7. The intraventricular injection of bradykinin (50 mug) caused a reduction in the amount of noradrenaline but not of 5-hydroxytryptamine (5-HT) in the brain stem; the amount of dopamine in the caudate nuclei was not affected.8. It is suggested that central cholinergic and adrenergic systems are activated by intraventricular bradykinin.
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PMID:Behavioural and somatic effects of bradykinin injected into the cerebral ventricles of unanaesthetized rabbits. 538 83

Intrinsic vascular responsiveness to norepinephrine, transmural electrical stimulation, 5-hydroxy-tryptamine, and vasopressin was studied in isolated helical cut strips of cystic artery (downstream branch of hepatic artery) from 120 subjects and related to blood pressure. Blood pressure, thickness of the tunica media, and passive elastic properties of arterial strips were each significantly correlated with age. With the exception of blood pressure in the female subjects, it is doubtful that these relationships are of major biologic significance. Nevertheless, in subgroup formation, care was taken to control for age. Hypertension was arbitrarily defined in three different ways as: (a) two diastolic pressure measurements greater than or equal to 90 mm Hg (HT90); (b) two diastolic pressure measurements greater than or equal to 95 mm Hg (HT95); or (c) treatment for hypertension instituted by a physician 6 months to 2 years after arteries were studied (HTQ). In arteries of hypertensive female subjects, responsiveness to norepinephrine (and possibly to 5-hydroxytryptamine) was increased significantly over the first half of the dose-response curve, particularly in the arteries of HT95 and HTQ subjects. Responses to transmural electrical stimulation and vasopressin were not consistently different. Such differences were not seen in arteries of male subjects where, if anything, responsiveness to norepinephrine (but not 5-hydroxytryptamine) was decreased. The present observations were made in the absence of any substantive difference in arterial dimensions (e.g., cross-section area) or in the maximal response to norepinephrine. The data support the notion that, at least for female subjects, alteration in intrinsic vascular responsiveness may play a role in the pathogenesis of human essential hypertension.
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PMID:Relationship of blood pressure to the responsiveness of an isolated human artery to selected agonists and to electrical stimulation. 608 64

Isolated perfused kidneys from 4- to 6-month-old spontaneously hypertensive rats (SHR, Japanese strain) exhibit increased "vascular reactivity" to 5-hydroxytryptamine (5-HT) and a slower rate of development of tachyphylaxis to this substance when compared with kidneys from normotensive Wistar-Kyoto (WKY) rats. We investigated the possibility that the reduced rate of development of tachyphylaxis could be related to a interaction of 5-HT with adrenergic mechanisms or with endogenous 5-HT. Tachyphylaxis was induced by repeated administration of 5-HT to kidneys from SHR and WKY rats. This procedure did not affect vasoconstrictor responses evoked by norepinephrine. The development of tachypylaxis to 5-HT in kidneys from SHR and WKY rats was not changed by chemical sympathectomy with 6-hydroxydopamine. Treatment of SHR with para-chlorophenylalanine did not affect their blood pressure or the development of tachyphylaxis to 5-HT. These results indicate that delayed tachyphylaxis to 5-HT in kidneys of SHR is not due to an interference with adrenergic mechanisms and does not depend on endogenous 5-HT levels. The phenomenon represents an unusual modification of vascular smooth muscle exposed to chronic high pressure, but it is unlikely that the vasoconstrictor effects of 5-HT contribute to the maintenance of hypertension in the SHR.
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PMID:Tachyphylaxis to 5-hydroxytryptamine in perfused kidneys from spontaneously hypertensive and normotensive rats. 616 95

The serotonin (5-hydroxytryptamine, 5-HT) antagonist, ketanserin, has a high affinity for 5-HT2-receptors but it also binds to alpha 1-adrenoceptors. The compound (10 mg i.v.) lowered mean arterial pressure by 22% +/- 2% (mean +/- SEM, p less than 0.001) in 30 patients with essential hypertension. Measurements of heart rate, cardiac output, cardiac filling pressures, forearm blood flow, renal blood flow, and glomerular filtration rate revealed a hemodynamic pattern compatible with vasodilation of both resistance and capacitance vessels. This was accompanied by moderate reflex cardiostimulation. Ketanserin did not alter the pressor effect of bolus injections of (-)-phenylephrine hydrochloride (25, 50, 100, and 200 micrograms i.v.). Ketanserin also had a distinct hypotensive effect in four normotensive patients with autonomic insufficiency due to an efferent sympathetic lesion, who were unresponsive to phentolamine (20 mg i.v.). Thus, ketanserin in the dose we have used appears to lower blood pressure independently of alpha 1-adrenoceptor blockade. On the other hand, in patients with essential hypertension the antihypertensive effect of ketanserin was blunted by pretreatment with prazosin (12 mg/day). Therefore, a certain degree of alpha 1-adrenergic tone seems to be required for the compound to exert its full antihypertensive action. The findings are indirect evidence for a role of 5-HT in the maintenance of increased vascular resistance in essential hypertension. This may be related, at least in part, to the alleged amplifying effect of 5-HT on alpha 1-adrenoceptor-mediated vasoconstriction.
Hypertension
PMID:5-HT, alpha-adrenoceptors, and blood pressure. Effects of ketanserin in essential hypertension and autonomic insufficiency. 631 78

Plasma serotonin concentrations, assayed as plasma 5-hydroxyindoles (5-HI) and platelet 5-hydroxytryptamine (5-HT), were measured in 12 patients undergoing coronary artery graft surgery (group 1) and five patients undergoing valve replacement (group 2). Mean values of plasma 5-HI before cardiopulmonary bypass (CPB) were 29.8 +/- 2.0 ng ml-1 in group 1 and 30.6 +/- 2.8 ng ml-1 in group 2. No significant changes of plasma 5-HI occurred during or after CPB in either group. Although postoperative hypertension occurred in 75% of group 1 patients, no significant correlation was found between plasma 5-HI concentration and systolic blood pressure. A significant increase of platelet 5-HT occurred during bypass (327 ng/2 X 10(8) platelets increasing to 488 ng/2 X 10(8) platelets, p less than 0.01) but returned to baseline values postoperatively. We conclude that plasma 5-HI concentrations are not involved in the pathophysiology of postoperative hypertension following myocardial revascularization.
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PMID:Plasma serotonin concentrations during and after cardiac surgery. 653 5

In patients developing hypertension following coronary artery bypass surgery (CABG) the possible role of 5-hydroxytryptamine (5-HT; serotonin) was investigated by injecting ketanserin, a specific 5-HT2-receptor antagonist. Ketanserin was administered intravenously when intraarterial systolic blood pressure (SAP) exceeded 150 mm Hg either as a 10-mg bolus (group 1, N = 15), or as a 10-mg bolus followed by infusion of 4 mg/h for either 2.5 h (group 2, N = 15) or for 1 h (group 3, N = 10). In 33 patients (82.5%), SAP and diastolic arterial pressure decreased significantly within 5 min after the 10-mg bolus. In group 1, SAP gradually increased after 30-50 min but in groups 2 and 3 SAP remained normal. The triple index (TI) decreased significantly in all groups. Heart rate decreased slightly but significantly in groups 2 and 3. Central venous and left atrial pressures did not change substantially in any of the three groups. Cardiac output increased significantly (0.51 +/- 0.158 L/min); hence, systemic vascular resistance (SVR) decreased significantly (452.1 +/- 50.57 dyn . s . cm-5--group 3). No rebound increase in SAP occurred after terminating the infusions (groups 2 and 3). These findings indicate that 5-HT plays a role in the majority of patients who develop hypertension following CABG. The decrease of SVR without reflex tachycardia is a favorable effect of ketanserin.
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PMID:The use of ketanserin, a 5-hydroxytryptamine receptor antagonist, for treatment of postoperative hypertension following coronary artery bypass surgery. 660 Mar 82


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