Differential antagonism of alpha-1 and alpha-2 adrenoceptor-mediated pressor responses by urotensin I, a selective mesenteric vasodilator peptide.
In order to characterize the hemodynamic actions of urotensin I, a vasodilator peptide with selectivity for the mesenteric vascular bed, we studied its hypotensive effects and interference with alpha-1 and alpha-2 adrenergic vasoconstrictor responses in the rat. After i.v. administration in anesthetized rats, urotensin I (0.06-6 nmol/kg) produced a dose-dependent lowering of arterial blood pressure. At hypotensive doses, urotensin I was about 3 times more potent in antagonizing systemic pressor responses to the selective alpha-1 adrenoceptor agonist, phenylephrine, than responses to the nonselective adrenoceptor agonist, norepinephrine. Additional studies were performed on the blood-perfused mesenteric bed of the anesthetized rat and on the isolated rat superior mesenteric artery, using as tools phenylephrine, norepinephrine and the relatively selective alpha-2 adrenoceptor agonist, alpha-methylnorepinephrine. The selectivity of the three agonists for vascular alpha-1 and alpha-2 adrenoceptors in the blood-perfused mesenteric bed was confirmed using prazosin and yohimbine as selective antagonists of alpha-1 and alpha-2 adrenoceptors, respectively. Urotensin I diminished the maximum increase in perfusion pressure and shifted the log dose-response curves to the right for all three agonists. A marked selectivity of urotensin I for alpha-1 adrenoceptor-mediated responses was observed: IC30 values of the peptide for pressor responses to phenylephrine, norepinephrine and alpha-methylnorepinephrine were 0.05, 0.83 and greater than 6 nmol/kg, respectively. A less pronounced selectivity of urotensin I for alpha-1 adrenoceptor-mediated contractions could be demonstrated in isolated strips of the superior mesenteric artery of the rat.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D008771:Nordefrin / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D014579:Urotensins / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D010455:Peptides; D011942:Receptors, Adrenergic, alpha; D014579:Urotensins; D010656:Phenylephrine; D015016:Yohimbine; C029676:urotensin I; D008771:Nordefrin; D009638:Norepinephrine; D011224:Prazosin