Role of intrarenal alpha(2)-adrenoceptors in the renal responses to xylazine in rats

This study examined the contribution of intrarenal alpha(2)-adrenoceptor me chanisms to the enhanced urine flow rate (V) and urinary sodium excretion ( UNaV) responses in ketamine-xylazine-anesthetized rats. Ten minutes after l eft renal artery (LRA) injection, the alpha(2)-adrenoceptor antagonist yohi mbine (5 mu g) significantly decreased V from 58 +/- 8 to 35 +/- 7 mu l.min (-1).g kidney wt(-1) and UNaV from 2.8 +/- 0.4 to 2.1 +/- 0.4 mu eq.min(-1) .g kidney wt(-1) without altering right kidney function. The renal effects of the LRA injection of yohimbine were completely abolished in chronic bila terally renal-denervated (RDNX) rats. In RDNX rats, a higher LRA dose of yo himbine (15 mu g) significantly reduced left and right kidney V, with no ef fects on UNaV. In separate bladder-catheterized rats, yohimbine (0.5 mg/kg) , 20 min after intravenous injection, significantly decreased V from 63 +/- 9 to 13 +/- 2 mu l.min(-1).g kidney wt(-1) and UNaV from 4.5 +/- 0.5 to 1. 1 +/- 0.1 mu eq.min(-1).g kidney wt(-1). In RDNX rats, this dose of yohimbi ne reduced V and UNaV, but the magnitude was blunted compared with intact r ats. In contrast, 0.1 mg/kg iv yohimbine significantly reduced V and UN,V t o similar magnitudes in intact and RDNX groups. Together, these findings in dicate that intravenous xylazine acts by renal nerve-dependent and -indepen dent mechanisms to enhance renal excretory function in ketamine-anesthetize d rats. Because the effects of the LRA dose of yohimbine were abolished in renal-denervated animals, it appears that xylazine has a direct renal actio n to augment the renal excretion of water and sodium via a presynaptic alph a(2)-adrenoceptor pathway that inhibits the release of neurotransmitters fr om renal sympathetic nerve terminals.