Central and peripheral actions of alpha 2-adrenergic agonists on renal function in Long-Evans and Brattleboro rats.
The effects of 3 alpha 2-adrenergic receptor agonists on renal function in vasopressin (AVP)-deficient Brattleboro (DI) rats were evaluated. The aim of this study was to determine the relative contribution of central versus peripheral alpha 2-adrenoceptors in mediating diuresis and natriuresis, as well as the role of alpha 2-adrenoceptors in antagonizing the actions of AVP. In addition to the studies of renal function, the effects of AVP deficiency on renal alpha 2-adrenoceptor affinity and number was evalauted along with determination of peripheral catecholamine stores. The centrally acting alpha 2-adrenergic agonists guanabenz and guanfacine significantly increased urine output and sodium excretion in Long-Evans (LE) rats. Guanabenz and guanfacine increased urine output in DI rats but failed to increase sodium excretion. The polar alpha 2-adrenergic agonist, ST-91, increased sodium excretion in both LE and DI rats, however, at a dose of 1.0 mg/kg urine output was significantly decreased in DI rats. The 3 alpha 2-adrenergic agonists increased potassium excretion in LE rats, but at the 1.0-mg/kg dose of guanabenz and ST-91, potassium excretion was significantly inhibited in DI rats. Renal alpha 2-adrenergic receptors and norepinephrine stores were not altered in DI rats. Adrenal NE stores were significantly elevated in DI rats relative to LE rats. The results of this study suggest that in the absence of AVP, centrally acting alpha 2-adrenergic agonists have limited natriuretic action, although peripheral activation of alpha 2-adrenoceptors is sufficient to elicit natriuresis irrespective of the presence of AVP. The chronic deficiency of AVP does not alter renal alpha 2-adrenergic receptor number, but the natriuretic and kaliuretic actions of alpha 2-adrenergic agonists are altered in DI rats.
Dawson
R
R
Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville.
Wallace
D R
DR
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004326:Drinking / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007677:Kidney Function Tests; D008297:Male; D011188:Potassium / Q000652:urine; D051381:Rats; D011910:Rats, Brattleboro; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D012964:Sodium / Q000652:urine; D013045:Species Specificity; D014563:Urodynamics / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D002395:Catecholamines; D011942:Receptors, Adrenergic, alpha; D012964:Sodium; D011188:Potassium