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

Unilateral microinjections of quipazine (0.9 micrograms in 50 nl) into the subretrofacial nucleus produced hypertension and a slight tachycardia associated with an increase in renal sympathetic nerve activity. Microinjections of quipazine lateral, caudal or rostral to this nucleus failed to alter blood pressure and heart rate. Similarly, microinjections of l-glutamate (3 nmol in 15 nl) into the subretrofacial nucleus elicited hypertension, tachycardia and renal sympatho-excitation. The magnitude of the pressor response to quipazine was smaller than the response elicited by l-glutamate but its duration was longer. Microinjections of quipazine into the lateral tegmental field at l-glutamate hypertensive sites failed to alter arterial blood pressure and heart rate. In contrast, microinjections of quipazine into the caudal ventrolateral medulla or into the nucleus tractus solitarii produced hypotension and sympatho-inhibition. These effects were prevented by microinjections of the 5-HT2 receptor antagonists, LY 53857 or BW 501C. The present results indicate that stimulation of 5-HT2 receptors of the subretrofacial nucleus produces hypertension and sympatho-excitation whereas stimulation of 5-HT2 receptors in the caudal ventrolateral medulla and in the nucleus tractus solitarii produces hypotension and sympatho-inhibition.
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PMID:Cardiovascular effects of microinjections of quipazine into nuclei of the medulla oblongata in anaesthetized cats: comparison with L-glutamate. 135 48

1. The abilities of various serotonergic drugs to bind with the 5-HT receptor of Ascaris suum muscle and to affect cyclic AMP levels in muscle tissue were examined. 2. Ligands which selectively interact with either the 5-HT1 or the 5-HT2 receptor in mammalian systems interact with the 5-HT receptor from A. suum muscle and increase cyclic AMP levels. 3. No binding of 5-HT3 ligands to 5-HT receptors from A. suum muscle was observed. 4. The 5-HT receptor of A. suum muscle should be called the 5-HTN (for Nematoda) receptor because its pharmacological and biochemical behaviors were different from those of mammalian 5-HT receptors.
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PMID:Identification of a novel 5-HTN (Nematoda) receptor from Ascaris suum muscle. 135 23

Quipazine (0.5 mg/kg i.v.) produced a sustained pressor response and an increase in splanchnic nerve activity in intact as well as in baroreceptor-denervated cats without causing a significant change in heart rate. These effects were prevented by the 5-HT2 receptor antagonists, ritanserin (0.5 mg/kg i.v.) or BW 501 C (0.5 mg/kg i.v.). Quipazine induced an hypertensive response and an increase in splanchnic discharge in cats pretreated with prazosin (0.1 mg/kg) or hexamethonium (10 mg/kg i.v.). Bilateral application of quipazine (25 micrograms/side) to the ventrolateral pressor area produced a rapid increase in mean blood pressure and in splanchnic discharge. Pretreatment with prazosin (0.1 mg/kg i.v.) abolished the hypertension but not the sympatho-excitatory effects of quipazine. Local application of the 5-HT2 receptor antagonists, LY53857 (10 micrograms/side) or cyproheptadine (10 micrograms/side), had no effects on blood pressure and splanchnic nerve activity but prevented or reversed the actions of locally applied quipazine. LY 53857 (10 micrograms/side) antagonized the sympatho-excitatory effects of systemically administered quipazine. These results indicate that the cardiovascular changes induced by quipazine in anaesthetized cats are mediated by central 5-HT2 receptors located in the ventrolateral pressor area and by peripheral vascular 5-HT2 receptors.
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PMID:Quipazine-induced hypertension in anaesthetized cats is mediated by central and peripheral 5-HT2 receptors: role of the ventrolateral pressor area. 167 91

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

Both intravenous and central administration of ketanserin, a 5-HT2 receptor antagonist, decrease blood pressure and sympathetic nerve activity, suggesting a central origin of its effects. However, ketanserin also possesses alpha 1-adrenoceptor blocking properties. Selective 5-HT2 receptor antagonists devoid of alpha 1-adrenoceptor blocking properties, e.g. LY 53857 and cinanserin, fail to reduce blood pressure and sympathetic nerve activity. In addition, 5-HT2 receptor agonists increase blood pressure and sympathetic nerve discharge. Therefore, it seems improbable that blockade of central 5-HT2 receptors alone could lead to a reduction in blood pressure. In contrast, the selective 5-HT1A receptor agonists 8-OH-DPAT and flesinoxan decrease blood pressure and heart rate by a centrally-mediated decrease in sympathetic tone and an increase in vagal tone. The sympatho-inhibitory effects of 5-HT1A receptor agonists result from the stimulation of postsynaptic 5-HT1A receptors within the ventrolateral pressor area. These results suggest that selective 5-HT1A receptor agonists acting in the central nervous system could be developed for the treatment of hypertension. Indeed, drugs such as flesinoxan and urapidil are effective in this setting.
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PMID:Central 5-hydroxytryptamine (5-HT) receptors in blood pressure regulation. 181 50

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

Ketanserin is a 5-HT2 receptor antagonist without partial agonist properties which also possesses weak alpha 1-adrenoceptor antagonistic activity, which may explain its antihypertensive mechanism of action in patients with essential hypertension. It also inhibits the effects of serotonin on platelets in cardiovascular disease, inhibits vasoconstriction caused by the amine, and when administered intravenously improves some haemorheological indices in patients with ischaemic diseases. The antihypertensive effect of oral ketanserin 40 mg twice daily is comparable with that of total daily doses of metoprolol 200 mg, propranolol 160 mg, captopril 100 mg, enalapril 20 mg, hydrochlorothiazide 50 mg, or alpha-methyldopa 1000 mg and is achieved without adverse effect on plasma lipoproteins or carbohydrate metabolism in patients with concomitant diabetes mellitus. Evidence from prospective studies suggests a greater antihypertensive efficacy in the elderly than in younger patients. In patients with intermittent claudication, results have been inconsistent in small studies, while a large study showed no improvement in pain-free walking distance but fewer amputations compared to placebo. In Raynaud's phenomenon symptomatic improvement relative to placebo was achieved in larger trials. Its role in preventing atherosclerotic complications requires further investigation. Ketanserin is reasonably well tolerated, the frequency of adverse effects being comparable with that of other antihypertensive drugs in controlled trials. Dizziness, tiredness, oedema, dry mouth and weight gain are the most commonly reported effects. Ketanserin prolongs QT interval in a dose-related manner, and when given in certain predisposing circumstances ventricular arrhythmias and syncope may occur. Administered intravenously, ketanserin 10mg followed by an infusion of 2 to 4 mg/h controls moderate to severe pre- and postoperative hypertension in most patients, acting as a balanced vasodilator, lowering cardiac pre- and afterload. Although the arrhythmogenic potential of ketanserin in patients receiving potassium-depleting diuretics requires suitable precautions, it appears that its antihypertensive activity is suited to the elderly provided plasma potassium concentrations are normal at the start of treatment and are maintained within the normal range.
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PMID:Ketanserin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in hypertension and peripheral vascular disease. 207 1

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 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

We investigated the effect of ICS 205-930 [(3 alpha-tropanyl)-1H-indole-3-carboxylic acid ester], a selective antagonist at 5-HT3 receptors, on the cardiogenic hypertensive chemoreflex in the anaesthetized dog. The reflex was elicited by injection of 5-HT (12.5-1600 micrograms) into the left cardiac ventricle and consisted of a dose-dependent systemic hypertension associated with a decrease in heart rate. ICS 205-930 (10, 30, and 100 micrograms/kg i.v.) caused a displacement to the right of both the dose-response curves of 5-HT-induced blood pressure increase and heart rate reduction. Its blocking effects upon the action of 5-HT could be surmounted by increasing the dose of the agonist. The selective 5-HT2 receptor antagonist, ketanserin (0.1 mg/kg i.v.) and the combined 5-HT1 and 5-HT2 receptor antagonist, methiothepin (0.1 mg/kg i.v.) had no influence on the hypertensive reflex. When the reflex was elicited by the ganglionic stimulant, 1,1-dimethyl-4-phenyl-piperazinium (DMPP; 100-1600 micrograms), ICS 205-930 had no blocking effect. The results suggest that the 5-HT-induced cardiogenic hypertensive chemoreflex is mediated by 5-HT3 receptors.
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PMID:Inhibition of the 5-HT-induced cardiogenic hypertensive chemoreflex by the selective 5-HT3 receptor antagonist ICS 205-930. 272 3


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