ALPHA-2-ADRENOCEPTOR ANTAGONISM ATTENUATES THE DIURETIC RESPONSE TO ACUTE COLD-EXPOSURE

Renal alpha2-adrenoreceptors modulate the hydrosmotic action of argini ne vasopressin (AVP) through suppression of AVP-stimulated adenosine 3 ',5'-cyclic monophosphate (cAMP) accumulation. Circulating catecholami nes, likely candidates for the endogenous ligand, are elevated during cold exposure (CE). These studies therefore tested the hypothesis that the diuresis observed with acute CE in rats is due in part to modulat ion of AVP's tubular action via alpha2-adrenoceptor activation. Subjec ts were five male Brattleboro homozygous diabetes insipidus (DI) rats (358 +/- 8 g) receiving chronic AVP replacement (1 mug.kg-1.day-1) and seven Long-Evans (LE) normal rats (395 +/- 5 g). In a CE protocol, ba seline measurements at room temperature (RT, 24 +/- 0.3-degrees-C) wer e followed by 60-min exposure to 5 +/- 0.5-degrees-C. Results were com pared with those from a RT time control protocol. The selective alpha2 -antagonist yohimbine (YOH; 10 mug.kg-1.min-1) or vehicle (VEH) was in fused throughout the CE and RT protocols. In VEH-infused rats, CE incr eased urine flow by 63 +/- 12 (DI rats) and 31 +/- 4 mul.min-1.100 g b ody wt-1 (LE rats), and mean arterial pressure by 36 +/- 1 (DI rats) a nd 32 +/- 2 mmHg (LE rats). The increased flow was largely a water diu resis, with changes in free water clearance averaging 45 +/- 11 (DI ra ts) and 28 +/- 3 mul.min-1.100 g body wt-1 (LE rats). YOH treatment co mpletely blunted the cold-induced diuresis in both strains but did not alter the CE-induced hypertension. Glomerular filtration rate was not affected by either CE or YOH infusion. These results in LE and AVP-re placed DI rats support the hypothesis that modulation of the hydrosmot ic action of AVP by alpha2-adrenoceptor activation mediates the diuret ic response to acute cold exposure. This alpha2-mediated response occu rs independently of changes in either mean arterial pressure or glomer ular filtration rate.