(Hypertension. 1995;26:1056-1059.)
© 1995 American Heart Association, Inc.
Articles |
5-Hydroxytryptamine2B Receptor Mediates Contraction in the Mesenteric Artery of Mineralocorticoid Hypertensive Rats
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-HT2B receptor, contracted
hypertensive arteries significantly (50% of 5-HT maximum) but not sham
arteries. Ketanserin (5-HT2A antagonist)
competitively inhibited contraction to 5-HT in arteries from
normotensive rats (-log dissociation constant [mol/L];
pKB=8.54) but not from hypertensive rats
(pKB >6.5). Moreover, contraction to kynuramine
was not blocked by ketanserin. Thus, under normal conditions,
5-HT2A receptors mediate contraction to 5-HT. However, in
DOCA-salt hypertension, ketanserin-insensitive 5-HT2
receptors, possibly 5-HT2B receptors, mediate mesenteric
arterial contraction to 5-HT.
Key Words: serotonin • hypertension, experimental • vasoconstriction • receptors, serotonin
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