The 5-hydroxytryptamine2A receptor is involved in (+)-norfenfluramine-induced arterial contraction and blood pressure increase in deoxycorticosterone acetate-salt hypertension.

The 5-hydroxytryptamine2A receptor is involved in (+)-norfenfluramine-induced arterial contraction and blood pressure increase in deoxycorticosterone acetate-salt hypertension. Research Abstract Details 

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The 5-hydroxytryptamine2A receptor is involved in (+)-norfenfluramine-induced arterial contraction and blood pressure increase in deoxycorticosterone acetate-salt hypertension. Abstract Text:

Wei Ni,Gregory D Fink,Stephanie W Watts,

The highly effective anorexigen (+)-fenfluramine was widely used to control body weight until the association with primary pulmonary hypertension and valvular heart disease. (+)-Norfenfluramine is the major hepatic metabolite of (+)-fenfluramine and is primarily responsible for the anorexic effect as well as side effects. We reported that (+)-norfenfluramine causes vasoconstriction and a blood pressure increase in rats with normal blood pressure via the 5-hydroxytryptamine (5-HT)2A receptor. With the knowledge that (+)-norfenfluramine also has affinity for 5-HT2B receptors and that arterial 5-HT2B receptor expression is up-regulated in deoxycorticosterone acetate (DOCA)-salt hypertension, we tested the hypothesis that (+)-norfenfluramine-induced vasoconstriction and pressor effects are potentiated in DOCA-salt hypertensive rats in a 5-HT2 receptor-dependent manner. Contractions of arteries were measured using an isolated tissue bath system or myograph. Mean arterial blood pressure was measured in chronically instrumented conscious rats. Effects of (+)-norfenfluramine in stimulating arterial contraction (leftward shift versus SHAM, aorta, 5.13-fold; renal artery, 1.95-fold; mesenteric resistance artery, 1.77-fold) and raising blood pressure were significantly enhanced in hypertension. In arteries from both normotensive and hypertensive rats, (+)-norfenfluramine-induced contraction in aorta was inhibited by 5-HT2A receptor antagonists, ketanserin and LY53857 (4-isopropyl-7-methyl-9-(2-hydroxy-1-meth ylpropoxycarbonyl)4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline), but not by the 5-HT2B receptor antagonist, LY272015 [6-chloro-5-methyl-N-(5-quinolinyl)-2,3-dihydro-1H-indole-1-carboxamide]. Ketanserin (3 mg/kg) reduced (+)-norfenfluramine-induced pressor response in both SHAM and DOCA rats. Our results demonstrate that (+)-norfenfluramine-induced arterial contraction and blood pressure increases are potentiated in DOCA-salt hypertensive rats. However, it is the 5-HT2A receptor and not the 5-HT2B receptor that participates in these effects.

The 5-hydroxytryptamine2A receptor is involved in (+)-norfenfluramine-induced arterial contraction and blood pressure increase in deoxycorticosterone acetate-salt hypertension. Publishing Authors By Initials

W Ni,GD Fink,SW Watts,

For similar vasoconstriction research abstracts see: vasoconstriction research

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The 5-hydroxytryptamine2A receptor is involved in (+)-norfenfluramine-induced arterial contraction and blood pressure increase in deoxycorticosterone acetate-salt hypertension. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: The Journal of pharmacology and experimental thera

VOLUME: 321

Page Numbers: 485-91

Journal Abbreviation:

ISSN: 0022-3565

DAY: 8

MONTH: 02

YEAR: 2007

The 5-hydroxytryptamine2A receptor is involved in (+)-norfenfluramine-induced arterial contraction and blood pressure increase in deoxycorticosterone acetate-salt hypertension. Information

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LANGUAGE: eng

NlmUniqueID: 376362

The 5-hydroxytryptamine2A receptor is involved in (+)-norfenfluramine-induced arterial contraction and blood pressure increase in deoxycorticosterone acetate-salt hypertension. Keywords Mesh Terms:

KEYWORDS: Vasoconstriction

MESH TERMS: drug effects

Chemical & Substance for Abstract: The 5-hydroxytryptamine2A receptor is involved in (+)-norfenfluramine-induced arterial contraction and blood pressure increase in deoxycorticosterone acetate-salt hypertension. Information

Substance Name: Sodium Chloride

Registry Number: 7647-14-5

Grant and Affiliation Information for The 5-hydroxytryptamine2A receptor is involved in (+)-norfenfluramine-induced arterial contraction and blood pressure increase in deoxycorticosterone acetate-salt hypertension.

AFFILIATION: Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824-1317, USA. niwei@msu.edu

Country: United States

AGENCY: United States NHLBI

GRANT: HL081115

ACRONYM: HL

MEDLINETA: J Pharmacol Exp Ther

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