Differential antagonism of alpha-1 and alpha-2 adrenoceptor-mediated vasoconstrictor responses by a vasodilator peptide, urotensin I: comparison with nifedipine.
We showed previously that in the dog, but not in the rat, Urotensin I, (UI), a neuropeptide with corticotropin releasing factor activity, selectively dilated the mesenteric circulation. Even in the rat, mesenteric arteries tested in vitro exhibited greater vasodilator responsiveness to UI than arterial preparations from elsewhere. In the rat in vivo, UI caused a preferential inhibition of alpha-1 adrenoceptor-mediated vasoconstriction, but it was unclear whether this provided an explanation for selective vasodilatation. The present study was done in the rat 1) to determine whether the effect of UI on alpha-1 adrenoceptors differed in regional vascular beds and 2) to compare the inhibitory action of UI on these responses with that of the calcium antagonist, nifedipine. The inhibitory actions of UI were similar, qualitatively and quantitatively, in both the blood-perfused mesenteric circulation and hindquarters of the urethane-anesthetized rat. In both systems, UI produced a greater inhibition of pressor responses to a selective alpha-1 adrenoceptor agonist, phenylephrine, than to norepinephrine or a selective alpha-2 adrenoceptor agonist, alpha-methylnorepinephrine. Pretreatment with prazosin, a selective alpha-1 adrenoceptor antagonist, reduced the antagonistic action of UI on norepinephrine responses in both vascular beds in vivo and in the rat mesenteric artery in vitro. In contrast, prazosin potentiated the inhibitory actions of nifedipine on pressor responses to norepinephrine in vivo without having significant effects on the antagonistic actions of nifedipine on norepinephrine responses in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
Bolt
G R
GR
Department of Pharmacology and Therapeutics, University of Calgary Faculty of Medicine, Alberta, Canada.
Itoh
H
H
Lederis
K
K
MacCannell
K L
KL
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013152:Splanchnic Circulation / Q000187:drug effects; D014579:Urotensins / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D010455:Peptides; D011942:Receptors, Adrenergic, alpha; D014579:Urotensins; D014665:Vasodilator Agents; C029676:urotensin I; D009543:Nifedipine; D009638:Norepinephrine; D011224:Prazosin