5-Hydroxytryptamine2B receptor mediates contraction in the mesenteric artery of mineralocorticoid hypertensive rats.
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 = alpha-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.
D000465:Algorithms; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003627:Data Interpretation, Statistical; D003900:Desoxycorticosterone; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D066298:In Vitro Techniques; D007537:Isometric Contraction; D007650:Ketanserin / Q000494:pharmacology; D007735:Kynuramine / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D044403:Receptor, Serotonin, 5-HT2B; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D012965:Sodium Chloride / Q000008:administration & dosage; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D000959:Antihypertensive Agents; D044403:Receptor, Serotonin, 5-HT2B; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D007735:Kynuramine; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D007650:Ketanserin