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 vascul ature and renal tubules play a major role in mediating antinatriuretic response to renal nerve stimulation as well as to the infusion of alp ha(1)-adrenoceptor agonist. In the present study intrarenal infusion o f alpha(1)-adrenoceptor agonist phenylephrine (0.25 mu g/kg/min) to In actin-anesthetized Sprague-Dawley rats produced approximately 50% redu ction in urine output, Na+ excretion and glomerular filtration rate wi thout causing significant alterations in mean blood pressure, heart ra te and fractional Na+ excretion. These changes were completely abolish ed by prior intrarenal infusion of prazosin (0.5 mu g/kg/min for 30 mi n). In separate groups of experiments, the animals received either a s elective irreversible alpha(1B)-adrenoceptor antagonist, SZL-49 cyclo[ 2,2,2]octa-2,5-diene-2-carbonyl)piperazine], or an alpha(1B)-adrenocep tor antagonist, chloroethylclonidine, intrarenally prior to phenylephr ine infusion. Neither SZL-49 nor chloroethylclonidine alone significan tly 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 u rine output, Na+ excretion and glomerular filtration rate. These resul ts demonstrate that phenylephrine decreases urine output and Na+ excre tion, mainly due to a reduction in glomerular filtration rate resultin g from activation of alpha(1A)-adrenoceptors, and that proximal tubula r alpha(1A)- or alpha(1B)-adrenoceptors do not appear to contribute to this response.