In vivo assessment of rat renal alpha adrenoceptors.
Despite a preponderance of alpha-2 adrenoceptors in homogenates of rat renal cortex, alpha-2 adrenoceptor agonists do not vasoconstrict the isolated buffer-perfused rat kidney. Both alpha-1 and alpha-2 adrenoceptor agonists can constrict the kidneys of dogs, cats and rabbits in vivo. Because alpha-2 adrenoceptor-mediated vasoconstriction is often difficult to demonstrate in vitro, and both subtypes of alpha agonists cause large increases in peripheral resistance in pithed rats, we tested the hypothesis that both alpha-1 and alpha-2 agonists would also constrict the rat kidney in vivo. Cannulation of the suprarenal artery and utilization of a high pressure liquid chromatography valve enabled random and reproducible intrarenal arterial bolus injections of agonists, and renal blood flow was monitored using Doppler flowmetry. Cirazoline, phenylephrine and norepinephrine bitartrate caused large renal vasopressor responses with minimal systemic effects. Although administered in a dosage range 100 to 1000 times that of alpha-1 agonists, the alpha-2 agonists (B-HT 920, UK 14,304 and guanabenz) produced only minimal renal vasoconstriction before systemic pressor effects. The low potency and efficacy of alpha-2 agonists could not be attributed to concomitant vasodilatory effects of these agents. Rat renal resistance vessels were less responsive to alpha-2 agonists than other species that have been examined. These studies are consistent with conclusions from in vitro examinations that only alpha-1 adrenoceptors mediate changes in renal vascular resistance and also autoradiographic studies reporting the localization of alpha-2 binding sites to rat renal tubules.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D000068438:Brimonidine Tartrate; D004305:Dose-Response Relationship, Drug; D006143:Guanabenz / Q000494:pharmacology; D006706:Homeostasis; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000032:analysis / Q000098:blood supply*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000032:analysis*; D014463:Ultrasonography; D014661:Vasoconstriction / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D007093:Imidazoles; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D000068438:Brimonidine Tartrate; C024763:talipexole; D006143:Guanabenz; C014282:cirazoline; D009638:Norepinephrine