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(Hypertension. 1995;26:1056-1059.)
© 1995 American Heart Association, Inc.

Articles

5-Hydroxytryptamine_2B Receptor Mediates Contraction in the Mesenteric Artery of Mineralocorticoid Hypertensive Rats

Stephanie W. Watts; Lisa Gilbert; R. Clinton Webb

From the Department of Pharmacology and Toxicology, Michigan State University, E Lansing (S.W.W.), and the Department of Physiology, The University of Michigan, Ann Arbor (L.G., R.C.W.).

Abstract Vascular responsiveness to 5-hydroxytryptamine (5-HT) is dramatically increased in hypertension. The hypothesis that augmented vasoconstriction to 5-HT in hypertension is due to a change in receptor subtype on vascular myocytes was tested. Mesenteric arteries from deoxycorticosterone acetate (DOCA)-salt hypertensive (systolic blood pressure >180 mm Hg) and sham normotensive (systolic blood pressure <130 mm Hg) rats were mounted in isolated tissue baths for measurement of isometric contractile force. The receptor mediating contraction in isolated mesenteric arteries from sham and DOCA-salt hypertensive rats is a member of the 5-HT₂ family based on rank order of agonist potency (5-HT=-methyl-5-HT [5-HT₂ receptor agonist]>tryptamine>5-hydroxykynuramine). 5-HT was approximately 10-fold more potent in contracting mesenteric arteries from DOCA-salt hypertensive rats compared with arteries from sham normotensive rats. The tryptophan metabolite kynuramine, which possesses significant contractile activity at the 5-HT_2B receptor, contracted hypertensive arteries significantly (50% of 5-HT maximum) but not sham arteries. Ketanserin (5-HT_2A antagonist) competitively inhibited contraction to 5-HT in arteries from normotensive rats (-log dissociation constant [mol/L]; pK_B=8.54) but not from hypertensive rats (pK_B >6.5). Moreover, contraction to kynuramine was not blocked by ketanserin. Thus, under normal conditions, 5-HT_2A receptors mediate contraction to 5-HT. However, in DOCA-salt hypertension, ketanserin-insensitive 5-HT₂ receptors, possibly 5-HT_2B receptors, mediate mesenteric arterial contraction to 5-HT.

Key Words: serotonin • hypertension, experimental • vasoconstriction • receptors, serotonin

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