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

Serotonin (5-hydroxytryptamine; 5-HT) is widely distributed in the body and subserves many functions. Tissue specificity of action is aided by differential receptor structure and function; the type 2 (5-HT2) receptor mediates arterial constriction and platelet aggregation. Very little serotonin is free in plasma, most being platelet-bound; however, local platelet activation and consequent serotonin release can present free serotonin to peripheral tissues. Serotonin, acting via the 5-HT2 receptor, can contribute to a range of cardiovascular problems, including portal hypertension, Raynaud's phenomenon, carcinoid flushes, preeclampsia, hypertension, arterial atheroma, and restenosis after angioplasty or thrombolysis. 5-HT2 antagonists have a potential therapeutic role in all these conditions. The diversity of such syndromes requires that the term "vascular protection" should not be applied loosely, but must always be precisely defined. Future 5-HT2 antagonists will probably be of two kinds: (a) with weak accompanying alpha 1 antagonism where blood pressure reduction is needed; and (b) as "pure" 5-HT2 antagonists, for use where arterial pressure falls are best avoided.
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PMID:Serotonergic type-2 (5-HT2) antagonists: a novel class of cardiovascular drugs. 171 73

Principal objectives in obesity management comprise the prevention of weight gain, the promotion of weight loss, and the treatment of obesity-related complications, including diabetes, hypertension, and depression. Serotonin agonists reduce food intake. The resultant weight loss is variable and there appears to be no way of predicting good responders, nor is there evidence that additional weight loss attributable to drug therapy is sustained once treatment is discontinued, although nonpharmacological strategies for preventing weight regain are worthy of exploration. Serotonin agonists are of clinical value if there is a short-term need for weight reduction or if long-term pharmacotherapy can be justified. This implies that sometimes the dangers of the obese state outweigh the potential hazards of drug treatment. Clearly, if the same agent also improves diabetic control, blood pressure, or depression then a longer term usage is more readily justified. The extent to which this may be achieved by the currently available 5-HT agonists is discussed.
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PMID:Appraisal of the clinical value of serotoninergic drugs. 172 33

Hypertension, a condition characterized by narrowing of the arteriolar lumen, is related in part to vasoconstriction and in part to vascular hypertrophy. Complex and interlocking mechanisms involving the autonomic nervous system and both circulating and local vasoconstrictor and vasodilator hormones contribute to this narrowing. Endothelin, 5-HT (serotonin), the kinins and ouabain may all participate by altering sodium, potassium and calcium fluxes in vascular smooth muscle cells. Recently the concept of insulin resistance as a mechanism of hypertension has emerged. Insulin may be a vascular growth factor as well as a local hormone facilitating a rise in intracellular sodium concentration. The observation that ACE inhibitors lower BP when plasma renin and angiotensin levels are low has led to an increased interest in local non-circulating renin-angiotensin systems. These systems probably influence arteriolar tone as well as vascular hypertrophy, and their inhibition leads to reduction in BP and some reversal of arteriolar thickening. Thus the ACE inhibitors represent a logical and effective method of treating hypertension and their use is likely to increase in the next few years.
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PMID:The mechanisms of hypertension and the role of ACE inhibitors. 179 16

Serotonin, a release product of activated platelets, stimulates proliferation and prostaglandin synthesis in cultured smooth muscle-like glomerular rat mesangial cells by activation of phospholipase and protein kinase C. To further characterize the signaling mechanisms used by serotonin, we monitored its effects on intracellular free Ca2+, pH, and membrane potential of cultured rat mesangial cells with sensitive fluorometric techniques. Activation of a 5-HT2 receptor, blocked by the specific receptor antagonists ketanserin and ritanserin, triggered immediate discharge of intracellular Ca2+ stores. The resulting rise of cytosolic free Ca2+ was accompanied by simultaneous membrane depolarization and followed within 30-60 seconds by prolonged cytosolic alkalinization. Depolarization and cytosolic free Ca2+ elevation were persistent in the continued presence of serotonin and were rapidly reversed by competitive receptor displacement with ketanserin or ritanserin. Depolarization is secondary to enhanced Cl- conductance, whereas it is relatively independent of Na+, K+, and Ca2+ fluxes. The putative Cl- channel is regulated by Ca2+ since ionomycin and other stimuli of cytosolic free Ca2+ mimic the effects of serotonin on membrane potential, whereas serotonin-induced depolarization is blunted in cells pretreated with the intracellular Ca2+ chelator BAPTA. Cytosolic alkalinization occurs in HCO3(-)-free solutions resulting from enhanced activity of a Na(+)-H+ exchanger and blocked by extracellular Na+ removal or amiloride. In the presence of HCO3-, serotonin elicits a persistent acidification, revealing simultaneous enhancement of a Na(+)-independent Cl(-)-HCO3- countertransport. These findings indicate multiple pathways for contraction and long-term functional changes induced by serotonin in mesangial cells, with potential relevance to glomerular and systemic hypertension.
Hypertension 1991 Feb
PMID:Serotonin and the glomerular mesangium. Mechanisms of intracellular signaling. 184 41

Pathological, muscular arteries (common and superficial femoral [FC, FS], anterior and posterior tibial [TA, TP] arteries) of patients suffering from arteriosclerosis obliterans (ASO), thromboangiitis obliterans (TAO), and diabetes mellitus (DIA), removed during amputation of the lower limb were studied as isolated organs. The vessels were cut into transverse rings and contractile force was measured isometrically. The total number of used rings was 828. The following agonists were applied: KCl (80 mM), serotonin (5-HT) (10 microM), prostaglandin F2 alpha (PGF2 alpha) (0.1 mM) or phenylephrine (PE) (10 microM). It was established that applying KCl, 5-HT or PGF2 alpha, the majority of arterial rings display a contraction, but most of the preparations (66%) give no response against PE. The measure of contraction depends on the diagnosis (TAO greater than ASO greater than DIA), on the age of patient and also the anatomical location of the artery in the case of TAO (TP greater than greater than TA), on the associated hypertension in the case of ASO (normotensive greater than hypertensive) and finally on the time elapsed between the operation and usage of preparation if the agonist is KCl. As a conclusion, despite the terminal clinical stage the majority of studied human arteries retained at least a part of their functional integrity.
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PMID:[Experiences with isolated organ studies on pathological human arteries]. 187 91

Serotonin (5-HT) is a potent bioactive substance known to function through a number of different receptor types and subtypes. In our attempt to develop new agents that would interact selectively at certain 5-HT receptors, especially the 5-HT1A subtype, 8-hydroxy-2-di-n-propylamino tetralin (8-OH-DPAT) served as a template for the design of novel agents sharing aspects of the pharmacophore of 8-OH-DPAT and 5-HT. 5-HT contains no center of asymmetry, and 8-OH-DPAT shows only very modest stereospecificity for 5-HT1A receptors. To develop agents having enhanced potency and selectivity for the 5-HT1A site, several ring systems offering enhanced conformational rigidity which approximate the oxygen to nitrogen interatomic distances of 8-OH-DPAT and (to a lesser extent) 5-HT were synthesized. Exemplary ring systems include the 8-alkoxy-hexahydroindeno[1,2-c]pyrrole, 5-alkoxy-hexahydro-1H-indeno-[2,1-c]pyridine, and 9-alkoxy-hexahydro-1H-benz[e]isoindole systems. These conformationally restricted molecules demonstrated moderate stereospecificity in their interaction with the 5-HT1A binding site, which was enhanced in compounds with larger nitrogen substituents. Appropriate choice of such derivatives led to highly potent compounds selective for 5-HT1A sites compared with their activity at other 5-HT and/or adrenergic receptors. The pharmacological profile of compounds which appear to act as agonists at 5-HT1A receptors in the central nervous system to lower blood pressure in animal models of hypertension is presented.
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PMID:Molecular design of novel ligands for 5-HT1A receptors. 188 79

The goal of this study was to determine whether responses of the basilar artery to products released by platelets are altered during chronic hypertension. The diameter of the basilar artery was measured using intravital microscopy in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) (6-8 months old) in response to adenosine 5'-diphosphate (ADP), serotonin, and the thromboxane analogue, U-46619. Dilatation of the basilar artery in response to nitroglycerin was also examined in WKY and SHR. Topical application of ADP (10 and 100 microM) produced only minimal changes in diameter of the basilar artery in WKY (3 +/- 1% and 1 +/- 1%, respectively) and SHR (-0.5 +/- 2% and -2 +/- 3%, respectively) (P greater than 0.05 vs WKY). Nitroglycerin, however, produced potent vasodilatation in WKY and SHR. Constriction of the basilar artery in response to serotonin was potentiated in SHR compared to WKY. Serotonin (0.1 and 1.0 microM) constricted the basilar artery by 11 +/- 2% and 20 +/- 2%, respectively, in WKY and by 29 +/- 3% and 40 +/- 3%, respectively, in SHR (P less than 0.05 vs WKY). In contrast, the thromboxane analogue (U-46619) (0.1 and 1.0 microM) produced similar constriction of the basilar artery in WKY (13 +/- 1% and 18 +/- 2%, respectively) and in SHR (14 +/- 3% and 21 +/- 6%, respectively). Thus, augmented vasoconstriction during chronic hypertension was specific for serotonin. Next, we examined the role of the cyclooxygenase pathway in responses of the basilar artery to ADP and serotonin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Responses of the basilar artery to products released by platelets during chronic hypertension. 190 15

The 5-HT2 antagonist ketanserin inhibited salt appetite induced by subchronic deoxycorticosterone acetate (DOCA) treatment, as well as salt appetite induced by sodium depletion (which is governed by the synergy of aldosterone and angiotensin in the brain). The effect of ketanserin was more evident following intraperitoneal than intracerebroventricular injection. On the other hand, ketanserin did not inhibit either salt intake induced by intracranial renin injection, or the need-free salt intake of the multidepleted female rat, which is not dependent on the renin-angiotensin-aldosterone system. These findings suggest that the antinatriorexic action of ketanserin is selective for the mineralcorticoid mechanisms controlling salt appetite. Ritanserin, too, a potent 5-HT2 antagonist showing a different receptor selectivity profile from that of ketanserin, suppressed DOCA-induced salt appetite, thus supporting the involvement of 5-HT receptors in the antinatriorexic action. DOCA treatment alters serotonin metabolism in the central nervous system and it has been proposed that changes in 5-HT metabolism may be important in the genesis of DOCA-induced hypertension. The present results indicate that ketanserin inhibits DOCA-induced salt appetite and suggest that serotoninergic mechanisms might be involved in the elicitation of mineralocorticoid-induced salt appetite.
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PMID:Effect of the 5-HT2 antagonist ketanserin on salt appetite in the rat. 192

Eleven coarctation hypertensive (CH), twelve sham control (C), and seven one-kidney, one-clip (1K,1C) rats were used to examine the role of pressure and the endothelium in vascular sensitivity changes to acetylcholine (ACh), serotonin (5-HT), and norepinephrine (NE) in chronic arterial hypertension. Terminal mean carotid artery pressures were CH = 156 +/- 5 mmHg, C = 99 +/- 3 mmHg, and 1K,1C = 159 +/- 5 mmHg. Femoral artery pressures were CH = 100 +/- 3 mmHg, C = 98 +/- 4 mmHg, and 1K,1C = 154 +/- 4 mmHg, respectively. Isometric tension recordings were made from helically cut strips of thoracic and abdominal aortas, with and without functional endothelium, from the three groups of rats. Sensitivity to relaxation by acetylcholine, expressed as -log of 50% effective dose, was significantly depressed in thoracic aortas from CH and 1K,1C rats and abdominal aortas from 1K,1C rats but not from abdominal aortas of CH rats. A similar relationship between the groups was seen for 5-HT contractions. Sensitivity to NE was enhanced in thoracic and abdominal aortas of hypertensive rats. Inactivation of aortic endothelia abolished ACh responses, did not alter 5-HT relationships between the three groups, and abolished the differences in sensitivity to NE in thoracic aortas. The data suggest that pressure and the endothelium may play a role in vascular sensitivity changes in hypertension.
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PMID:Endothelium in functional aortic changes of coarctation hypertension. 201 22

The pathogenesis of primary Raynaud's phenomenon remains an enigma. Most evidence favors a local abnormality in the digital arteries as opposed to an increased activity of the sympathetic nervous system. The local fault may involve the alpha 2-adrenergic receptors, which are most important in reflex sympathetic vasoconstriction. Cooling blood vessels increase the sensitivity of alpha 2-adrenergic receptors, increased levels of alpha 2-adrenergic receptors are present in primary Raynaud's disease, and patients show an increased sensitivity to alpha 2-adrenergic receptor agonists on finger blood flow. Serotonin has also been implicated, but the evidence is not compelling. In secondary Raynaud's phenomenon, vasospastic attacks can often be explained by a low arterial distending pressure, a thickened vessel wall, or absence of beta-adrenergic receptor activity. Diagnosis of primary Raynaud's disease relies on a typical history and normal physical examination, laboratory studies, and nailfold capillaroscopy. Finger systolic blood pressures during local cooling with ischemia may be helpful to document vasospastic attacks but does not distinguish primary from secondary Raynaud's phenomenon. The treatment of Raynaud's phenomenon is usually conservative. Pavlovian conditioning or biofeedback may be beneficial. When drug therapy is necessary, the calcium channel entry blocker nifedipine or sympatholytic agents have been shown to decrease the frequency and duration of vasospastic attacks in about two thirds of patients, although subjective improvement does not usually correlate with objective testing. Direct-acting vasodilators have not been shown to be of definite benefit. New therapies include prostaglandins, captopril, and the serotonergic antagonist ketanserin. Surgical sympathectomy has not been beneficial.
Hypertension 1991 May
PMID:Raynaud's phenomenon. An update. 202 4


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