Differential inhibition of alpha adrenoceptor-mediated pressor responses by rat atrial natriuretic peptide in the pithed rat.
Previous investigations have shown that rat atrial natriuretic peptide (r-ANP,5-28, atriopeptin III), antagonizes the effects of various pressor hormones (angiotensin II, vasopressin and norepinephrine) but is ineffective against pressor responses to acute spinal cord stimulation. Because the latter are believed to be mediated by intrajunctional alpha-1 adrenoceptors, whereas the others are thought to involve mainly extrajunctional receptors, we explored the possible specificity of r-ANP for alpha adrenoceptor subtypes, by comparing r-ANP, the calcium channel blocker nifedipine and the vasodilator sodium nitroprusside in their ability to inhibit pressor responses to the alpha-2 and alpha-1 adrenoceptor agonists, clonidine and phenylephrine, in pithed, vagotomized rats. Acute pressor responses to bolus-injected clonidine were dose-dependently attenuated by both r-ANP (up to 21%) and nifedipine (up to 37%), but acute pressor responses to phenylephrine were unaffected. Sodium nitroprusside inhibited pressor responses to clonidine (up to 67%) and phenylephrine equally (up to 66%). Pressor responses during constant infusions of clonidine and phenylephrine were attenuated similarly by r-ANP and nifedipine. This pattern of results, alpha-2 adrenoceptor specificity during immediate pressor responses but not during sustained pressor responses, suggests that r-ANP, like nifedipine, attenuates those adrenoceptor-mediated pressor responses which depend on slow transmembrane calcium fluxes.
D000317:Adrenergic alpha-Antagonists; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology; D003655:Decerebrate State; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000317:Adrenergic alpha-Antagonists; D009599:Nitroprusside; D010656:Phenylephrine; D009320:Atrial Natriuretic Factor; D009543:Nifedipine; D003000:Clonidine