IDENTIFICATION OF ALPHA(1)-ADRENOCEPTOR SUBTYPES INVOLVED IN THE ANTINATRIURETIC RESPONSE TO INTRARENAL INFUSION OF PHENYLEPHRINE

It is reported that alpha(1)-adrenoceptors located in the renal vasculature and renal tubules play a major role in mediating antinatriuretic response to renal nerve stimulation as well as to the infusion of alpha(1)-adrenoceptor agonist. In the present study intrarenal infusion of alpha(1)-adrenoceptor agonist phenylephrine (0.25 mu g/kg/min) to Inactin-anesthetized Sprague-Dawley rats produced approximately 50% reduction in urine output, Na+ excretion and glomerular filtration rate without causing significant alterations in mean blood pressure, heart rate and fractional Na+ excretion. These changes were completely abolished by prior intrarenal infusion of prazosin (0.5 mu g/kg/min for 30 min). In separate groups of experiments, the animals received either a selective irreversible alpha(1B)-adrenoceptor antagonist, SZL-49 [1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-bicyclo[2,2,2]octa-2,5-diene-2-carbonyl)piperazine], or an alpha(1B)-adrenoceptor antagonist, chloroethylclonidine, intrarenally prior to phenylephrine infusion. Neither SZL-49 nor chloroethylclonidine alone significantly altered glomerular filtration rate and renal electrolyte excretion. However, SZL-49 (0.15 mu g/kg/min), but not chloroethylclonidine (50 mu g/kg/min), completely abolished phenylephrine-induced changes in urine output, Na+ excretion and glomerular filtration rate. These results demonstrate that phenylephrine decreases urine output and Na+ excretion, mainly due to a reduction in glomerular filtration rate resulting from activation of alpha(1A)-adrenoceptors, and that proximal tubular alpha(1A)- or alpha(1B)-adrenoceptors do not appear to contribute to this response.