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

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

The effects of serotonin (5-hydroxytryptamine; 5-HT) on the cardiovascular system are complex. These effects, consisting of bradycardia or tachycardia, hypotension or hypertension, and vasodilation or vasoconstriction are mediated by three main sets of receptors called 5-HT1-like, 5-HT2, and 5-HT3. In addition, recent findings suggest the participation of a putative 5-HT4 receptor. Though selective 5-HT1A receptor agonists can lower heart rate (and arterial blood pressure), 5-HT usually lowers heart rate by eliciting an initial short-lasting hypotension due to bradycardia (von Bezold-Jarisch-like reflex) via 5-HT3 receptors located on sensory vagal nerve endings in the heart. Once this bradycardia reflex is suppressed--for example, during deep anesthesia, vagotomy, or spinal section--5-HT can increase heart rate in different species by a variety of mechanisms. Myocardial 5-HT1-like, 5-HT2, and 5-HT4 receptors appear to be involved in the cat, rat, and pig, respectively. 5-HT-induced tachycardia in the dog and rabbit is due mainly to release of catecholamines and involves 5-HT2 receptors on the adrenal medulla and 5-HT3 receptors on postganglionic cardiac sympathetic nerve fibers. Recently, 5-HT3 receptors also have been implicated in the 5-HT-induced tachycardia in the conscious dog. The blood pressure response to 5-HT is usually triphasic and consists of a von Bezold-Jarisch-like reflex, a middle pressor phase, and a longer-lasting hypotension. The pressor response is a consequence of vasoconstriction mediated via 5-HT2 receptors; however, vasoconstriction in the dog saphenous vein and cephalic arteries and arteriovenous anastomoses is due to stimulation of 5-HT1-like receptors. The depressor response exclusively involves 5-HT1-like receptors located at four different sites: (a) central nervous system (decrease in sympathetic and increase in vagal nervous activity), (b) sympathetic nerve terminals (reduction of transmitter release), (c) vascular smooth muscle (vasodilatation), and (d) vascular endothelium (release of a relaxant factor, probably nitric oxide). Arteriolar dilatation, together with the constriction of arteriovenous anastomoses, leads to an increase in nutrient (tissue; capillary) blood flow. The 5-HT1-like receptors are heterogeneous in nature; however, apart from the resemblance of the central nervous system 5-HT1-like receptor causing hypotension and bradycardia to the 5-HT1A binding subtype, the relationship of the other 5-HT1-like receptors to 5-HT1 binding subtypes is still debatable.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cardiovascular effects of serotonin agonists and antagonists. 170 84

Quipazine (0.5-2 mg/kg i.v.) produced transient hypotension and bradycardia followed by sustained hypertension and variable effects on heart rate in anaesthetized rats. The hypotension, bradycardia and sympatho-inhibitory effects of quipazine were attenuated by bivagotomy. In bivagotomized rats, the hypertension produced by quipazine was not modified by hexamethonium or prazosin but was abolished by ritanserin (1 mg/kg i.v.). In ritanserin-treated rats, section of the carotid sinus nerves and vagus nerves or ICS 205.930 (0.1 mg/kg i.v.) abolished the hypotensive, bradycardic and sympatho-inhibitory effects of quipazine; the action of quipazine was not reproducible in these rats. Quipazine also inhibited the Bezold-Jarish reflex elicited by 5-HT (20 micrograms/kg i.v.). In ICS 205.930-treated rats, the hypertension evoked by quipazine was associated with a reduction in splanchnic nerve activity due to stimulation of baroreceptors. The renin-angiotensin system is not involved in the hypertensive response. The increase in heart rate produced by quipazine in bivagotomized rats was reduced by ritanserin and tertatolol (0.1 mg/kg i.v.) and abolished by a combination of both drugs. We conclude that the bradycardic and sympatho-inhibitory effects of quipazine result from activation of 5-HT3 receptors located in the cardiopulmonary area and of carotid body chemoreceptors. The hypertension and tachycardia are mediated by vascular and myocardial 5-HT2 receptors. No evidence was obtained for a central sympatho-excitatory effect.
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PMID:The cardiovascular effects of quipazine are mediated by peripheral 5-HT2 and 5-HT3 receptors in anaesthetized rats. 212 77

Serotonin is a monoamine and is widely distributed in the human organism. Serotonin is synthesized from the amino acid tryptophane and is broken down via mono-amino-oxydase enzymes to 5-hydroxy-indol-acetic acid and by acetylizing and methylizing to melantonin. In 1986, a consensus concerning the classification of the serotonergic receptors was established. Three main classes were determined, viz: 5-HT1, 5-HT2 and 5-HT3. 5-HT1 receptors were further subdivided into A, B, C and D-receptors and, of these, the 5-HT1A-receptor is involved in the centrally mediated blood pressure control via reduction in the pre- and postganglionic sympathetic activity. The 5-HT2 receptors are primarily involved in control of peripheral blood pressure where agonizing results in vascular contraction of the large arteries and veins and thrombocyte aggregation. The 5-HT1 receptors are also involved peripherally in connection with release of relaxing factors derived from endothelium. In vitro and in animal experiments, it has been demonstrated that serotonin is capable of inducing arrhythmia and myocardial dysfunction via 5-HT3 receptors. Several preparations with effects on both the central and peripheral serotonergic receptors are already marketed for treatment of hypertension and other conditions.
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PMID:[Serotonin and cardiovascular control]. 221 14

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

The cardiovascular effects of 5-hydroxytryptamine (5-HT), consisting of bradycardia or tachycardia, hypotension or hypertension, and vasodilatation or vasoconstriction, are mediated by three main types of receptors called 5-HT1-like, 5-HT2, and 5-HT3. In intact animals 5-HT elicits a short-lasting bradycardia, accompanied by hypotension, via stimulation of 5-HT3 receptors located on sensory vagal nerve endings in the heart (Bezold-Jarisch reflex). The nature of 5-HT receptors mediating tachycardiac responses is species-dependent. Myocardial 5-HT1-like and 5-HT2 receptors subserve tachycardia in the cat and rat, respectively. Tachycardia in the dog and rabbit is due to a release of catecholamines effected via the 5-HT2 receptors on the adrenal medulla and the 5-HT3 receptors on postganglionic cardiac sympathetic nerve fibres, respectively. The receptors mediating tachycardia in the pig are unique as they do not resemble any of the three 5-HT receptors characterized so far. The blood pressure response to 5-HT is usually triphasic: initial short-lasting hypotension due to reflex bradycardia (via 5-HT3 receptors), a middle pressor phase (via 5-HT2 receptors), and a longer-lasting hypotension (via 5-HT1-like receptors). Vascular contraction by 5-HT is generally mediated by 5-HT2 receptors (located primarily on the large conducting vessels), though in some instances (e.g., dog saphenous vein, dog and human basilar artery, and porcine arteriovenous anastomoses) the contractile response is (also) mediated via 5-HT1-like receptors. Venous dilatation and arteriolar dilatation (leading to increased capillary ['nutrient'] blood flow) occur via 5-HT1-like receptors located mainly on the vascular smooth muscles but also on the endothelium; the smooth muscle and endothelial 5-HT1-like receptors seem to be heterogeneous. In addition, 5-HT can elicit vasodilatation and hypotension as a result of decreased sympathetic nervous tone by acting within the central nervous system and by inhibiting noradrenaline release by a presynaptic action. Both these effects also involve 5-HT1-like receptors that do not appear to be identical. Last, knowledge of the cardiovascular effects of 5-HT and the nature of the receptors involved should be helpful in developing 5-HT-related compounds that may be useful in the treatment of hypertension, migraine, and peripheral vascular diseases.
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PMID:Cardiovascular effects from stimulation of 5-hydroxytryptamine receptors. 267 Jul 24

Identification of 5-HT receptor subtypes--5-HT1A, 5-HT1B, 5-HT1C, 5-HT1D, 5-HT2 (possibly A and B), 5-HT3 subtypes, and possibly 5-HT4--has encouraged the manufacture of 5-HT receptor inhibitors with greater subtype specificity. However, it appears that the receptors interact, and drugs initially thought to be specific may have multiple actions. For some conditions such as anxiety/depression, almost all receptors are implicated. Clinical studies provide clear evidence that manipulation of the 5-HT system has a role in treating depression, anxiety, obsessional illness, migraine, and eating disorders. Interactions between the various receptor subtypes make it difficult to identify specific clinical functions. The 5-HT1A receptors may be involved in aggression, anorexia, and hypotension. The 5-HT1B receptors may be involved in aggression, while the 5-HT1C receptors may play a role in central aversion systems and anxiety/depression. The role of the 5-HT1D receptors remains speculative; 5-HT2 receptors appear to be involved in depression, anxiety, appetite, sleep, vasoconstriction, and hypertension. Many drugs that are effective in treating migraine are potent 5-HT2 antagonists. 5-HT3 antagonists at high doses are effective in treating nausea and at low doses in treating anxiety. Treatment of aggression, suicidal behaviour, addiction behaviour, memory impairment, dementia, and schizophrenia with 5-HT inhibitors requires further testing.
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PMID:Is there a relationship between serotonin receptor subtypes and selectivity of response in specific psychiatric illnesses? 269 41

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

We hypothesized that impaired cardiopulmonary reflexes but not altered baroreceptor reflexes precede deoxycorticosterone acetate (DOCA)-salt hypertension. Uninephrectomized rats were given either DOCA and 0.9% NaCl as drinking water, 0.9% NaCl alone, or tap water. We measured mean blood pressure, heart rate, and renal sympathetic nerve activity. After 8 days, mean blood pressure was not different in DOCA-salt and control rats. Volume-sensitive cardiopulmonary reflexes were tested by intravenous volume loading with saline (10% body weight in 15 minutes), which decreased renal sympathetic nerve activity without changing mean blood pressure or heart rate. This response was blunted in DOCA-salt rats. Chemosensitive cardiopulmonary reflexes were tested by 15-minute infusions of the serotonin 5-HT3 agonist phenylbiguanide, which decreased renal sympathetic nerve activity without changing mean blood pressure or heart rate. Sustained decreases in renal sympathetic nerve activity occurred during phenylbiguanide infusion in controls but were blunted over time in DOCA-salt rats. The arterial baroreflex responses to graded infusions of methoxamine and nitroprusside were analyzed by sigmoidal curve fitting. There were no differences in gain of renal sympathetic nerve activity or heart rate between the groups. Thus, DOCA-salt rats exhibit impaired cardiopulmonary reflexes before the onset of hypertension; the volume-sensitive reflexes are more severely affected than chemosensitive reflexes. The arterial baroreceptor reflex is unaltered. The decreased sensitivity of cardiopulmonary reflexes may contribute to DOCA-salt hypertension.
Hypertension 1994 Nov
PMID:Impaired cardiovascular reflexes precede deoxycorticosterone acetate-salt hypertension. 796 14

The carotid sinuses, one of the major sites of baroreceptor innervation, are also a common site of atherosclerotic lesions and platelet aggregation. The goal of the present study was to determine whether platelet activation in carotid sinuses causes reflex-mediated changes in renal sympathetic nerve activity and arterial pressure. Rabbit platelets were isolated, resuspended in Krebs' buffer, and activated by thrombin. Injection of activated platelets (3 x 10(8) platelets/mL) into the vascularly isolated carotid sinuses of anesthetized rabbits essentially eliminated sympathetic nerve activity and acutely decreased mean arterial pressure from 126 +/- 5 to 53 +/- 4 mm Hg (n=16; P < .05). Sympathetic activity and arterial pressure returned to control levels over a period of minutes despite sustained exposure to activated platelets. Injection of U-46619, a thromboxane analogue and vasoconstrictor, into carotid sinuses did not alter sympathetic activity or arterial pressure. However, serotonin (5-hydroxytryptamine [5-HT]), which is known to be released from activated platelets, and the 5-HT3 receptor agonist phenylbiguanide mimicked the effect of platelets. Furthermore, the platelet-induced reflex inhibition of sympathetic activity and hypotension were not altered by the cyclooxygenase inhibitor indomethacin but were attenuated significantly by 5-HT receptor antagonists. Platelet activation inhibited sympathetic activity to 5 +/- 2% of control in the absence of antagonists but to only 35 +/- 11 and 76 +/- 4% of control after selective blockade of 5-HT2 and 5-HT3 receptors with ketanserin and MDL-72222, respectively. The results indicate that (1) platelet activation in carotid sinuses triggers reflex inhibition of sympathetic nerve activity and hypotension; (2) the reflex is not caused by carotid vasoconstriction and is not mediated by prostanoids; and (3) the reflex is mediated by 5-HT acting primarily on 5-HT3 and to a lesser extent on 5-HT2 receptors. We speculate that this reflex may contribute to arterial pressure lability and susceptibility to stroke in patients with carotid atherosclerotic disease.
Hypertension 1996 Mar
PMID:Platelet activation in carotid sinuses triggers reflex sympathoinhibition and hypotension. 861 8


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