5-Hydroxytryptamine(2B) receptor mediates contraction in the mesenteric artery of mineralocorticoid hypertensive rats

S. W. Watts, L. Gilbert, R. C. Webb

Research output: Contribution to journalArticle

36 Scopus citations

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=α-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. Ketanserine (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, ketanserine- insensitive 5-HT2 receptors, possibly 5-HT(2B) receptors, mediate mesenteric arterial contraction to 5-HT.

Original languageEnglish (US)
Pages (from-to)1056-1059
Number of pages4
JournalHypertension
Volume26
Issue number6 II
DOIs
StatePublished - Jan 1 1995

Keywords

  • hypertension, experimental
  • receptors, serotonin
  • serotonin
  • vasoconstriction

ASJC Scopus subject areas

  • Internal Medicine

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