Renal alpha 1- and alpha 2-adrenoceptor mediated vasoconstriction in dogs.
Clonidine (C) and guanabenz (G) are both alpha 2-agonists. Whereas C has been reported to cause anti-natriuresis proportional to renal vasoconstriction with acute infusion, G increases sodium and water excretion with little change in renal blood flow (RBF). C-mediated vasoconstriction may involve alpha 1-receptors. RBF in anaesthetized dogs was measured electromagnetically. Boluses of phenylephrine (P), C and G were injected into the renal artery via a perfusion cannula. Responses were expressed as delta RBF. Then prazosin or yohimbine were administered intra-arterially and dose-response curves repeated. The shift in dose ratio (delta ED50 after prazosin/yohimbine) for P was 52.9, for C was 4.7 and for G was 0.62. G was a 10-fold weaker vasoconstrictor than C, but G was still effective when alpha 1-receptors were blocked. Ten-fold differences were found between P, C and G for dependence upon alpha 1-adrenoceptors. Denervation did not significantly shift the curves. Thus, postsynaptic alpha 2-receptors can contribute to renal vasoconstriction, but the receptors are either less numerous or less efficiently coupled to contractile elements than in other beds. Verapamil markedly attenuated responses to C and G. Since tubular alpha 1-receptors have also been implicated in sodium transport, C may be more prone than G to cause anti-natriuresis both through stimulated tubular reabsorption and renal vasoconstriction.
D000818:Animals; D002118:Calcium / Q000502:physiology; D003000:Clonidine / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006143:Guanabenz / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D015016:Yohimbine; D014700:Verapamil; D006143:Guanabenz; D003000:Clonidine; D002118:Calcium; D011224:Prazosin