Peripheral and central imidazoline receptor-mediated natriuresis in the rat.
On the basis of both radioligand and functional studies, the existence of a novel receptor that was unique from the alpha 2-adrenoceptor has become evident. Our initial studies contrasted the function of I1 imidazoline receptor agonists with that of purported alpha 2-adrenoceptor agonists in the kidney. The mechanism by which urine flow increased (osmolar vs free water clearance) as well as the effects of idazoxan, rauwolscine, a V2 vasopressin receptor antagonist, indomethacin pretreatment, and one-kidney one clip hypertension in rats were different following moxonidine when compared to an alpha 2-adrenoceptor agonist. This indicated two separate receptor systems. Subsequent studies determined that i.c.v. administration of moxonidine would also increase the urine flow rate by increasing osmolar clearance. This response to i.c.v. moxonidine differed from the response of an alpha 2-adrenoceptor agonist administered i.c.v.. Moreover, this effect of i.c.v. moxonidine was unique from that observed following the intrarenal infusion of moxonidine (Fig. 2). Denervation, intravenous prazosin, and i.c.v. idazoxan selectively blocked the effects of i.c.v. moxonidine. Intravenous idazoxan selectively blocked the response to intrarenal infusion of moxonidine. On the basis of the response to i.c.v. moxonidine in SH rats, the site(s) and/or receptor(s) responsible for blood pressure lowering were altered and those for increasing sodium excretion appear to be inactive. The significance of the findings in long-term regulation of blood pressure remain to be determined.
Department of Pharmacology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada. dsmyth@ms.umanitoba.ca
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D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D007093:Imidazoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D054755:Imidazoline Receptors; D007668:Kidney / Q000294:innervation / Q000502:physiology*; D009318:Natriuresis / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D011955:Receptors, Drug / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology*
D000959:Antihypertensive Agents; D007093:Imidazoles; D054755:Imidazoline Receptors; D018340:Receptors, Adrenergic, alpha-1; D011955:Receptors, Drug; C043482:moxonidine