title: Alpha 1-adrenoceptor blockade and altered renal alpha 2-adrenoceptors: a model(?) for the study of genetically altered alpha 2-adrenoceptors in hypertensive rats.
abstract: Renal nerve stimulation (RNS)-induced sodium retention is normally mediated by alpha 1-adrenoceptors. Clinically, chronic prazosin therapy increases rather than decreases sodium retention. In preliminary studies, chronic prazosin (3 days, 3 mg/kg per day) increased renal alpha 2-adrenoceptor density (mean +/- s.e.m., 153 +/- 14 versus 209 +/- 11 fmol/mg protein) in normal rats. We therefore postulated that following chronic prazosin treatment, alpha 2-adrenoceptors may mediate RNS-induced sodium retention. The effect of chronic prazosin pretreatment on the alpha-adrenoceptor subtype mediating RNS-induced antinatriuresis was studied in the perfused rat kidney. In control rats, subpressor levels of RNS (approximately 1 Hz, 10 V, 1 ms) decreased sodium and water excretion. Prazosin 28 nmol/l (alpha 1-blockade) reversed this effect of RNS. Yohimbine 300 nmol/l (alpha 2-blockade) had no effect. In rats treated with prazosin, RNS again decreased sodium and water excretion. In these rats, yohimbine as well as prazosin was necessary to reverse the effects of RNS. Thus, following prazosin pretreatment postjunctional alpha 2- as well as alpha 1-adrenoceptors mediated RNS-induced antinatriuresis. A similar function of the elevated renal alpha 2-adrenoceptors in genetic hypertension in rats could possibly explain the mechanism by which excess sodium retention occurs and thereby the elevation of blood pressure.
mesh_terms: D000818:Animals; D006973:Hypertension / Q000235:genetics* / Q000473:pathology; D007668:Kidney / Q000294:innervation*; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D012964:Sodium / Q000378:metabolism
chemical_list: D011942:Receptors, Adrenergic, alpha; D012964:Sodium; D011224:Prazosin