5-hydroxytryptamine2B receptor mediates contraction in the mesenteric artery of mineralocorticoid hypertensive rats

Stephanie W. Watts, Lisa Gilbert, R Clinton Webb

Research output: Contribution to journalArticle

35 Citations (Scopus)

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 Hood 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-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.

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

Fingerprint

Mineralocorticoids
Mesenteric Arteries
Serotonin
Ketanserin
Desoxycorticosterone
Kynuramine
Receptor, Serotonin, 5-HT2B
Arteries
Acetates
Salts
Blood Pressure
Hypertension
Blood Vessels
Serotonin 5-HT2 Receptor Antagonists
Receptor, Serotonin, 5-HT2A
Vasoconstriction
Tryptophan
Muscle Cells

Keywords

  • Hypertension, experimental
  • Receptors, serotonin
  • Serotonin
  • Vasoconstriction

ASJC Scopus subject areas

  • Internal Medicine

Cite this

5-hydroxytryptamine2B receptor mediates contraction in the mesenteric artery of mineralocorticoid hypertensive rats. / Watts, Stephanie W.; Gilbert, Lisa; Webb, R Clinton.

In: Hypertension, Vol. 26, No. 6 II, 01.12.1995, p. 1056-1059.

Research output: Contribution to journalArticle

@article{1ff09bfffec34c1297f74e4a335ac883,
title = "5-hydroxytryptamine2B receptor mediates contraction in the mesenteric artery of mineralocorticoid hypertensive rats",
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 Hood 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-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.",
keywords = "Hypertension, experimental, Receptors, serotonin, Serotonin, Vasoconstriction",
author = "Watts, {Stephanie W.} and Lisa Gilbert and Webb, {R Clinton}",
year = "1995",
month = "12",
day = "1",
language = "English (US)",
volume = "26",
pages = "1056--1059",
journal = "Hypertension",
issn = "0194-911X",
publisher = "Lippincott Williams and Wilkins",
number = "6 II",

}

TY - JOUR

T1 - 5-hydroxytryptamine2B receptor mediates contraction in the mesenteric artery of mineralocorticoid hypertensive rats

AU - Watts, Stephanie W.

AU - Gilbert, Lisa

AU - Webb, R Clinton

PY - 1995/12/1

Y1 - 1995/12/1

N2 - 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 Hood 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-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.

AB - 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 Hood 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-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.

KW - Hypertension, experimental

KW - Receptors, serotonin

KW - Serotonin

KW - Vasoconstriction

UR - http://www.scopus.com/inward/record.url?scp=0028865535&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028865535&partnerID=8YFLogxK

M3 - Article

VL - 26

SP - 1056

EP - 1059

JO - Hypertension

JF - Hypertension

SN - 0194-911X

IS - 6 II

ER -