Role of intrarenal a2-adrenoceptors in the renal responses to xylazine in rats

Menegaz, Rubia G., Daniel R. Kapusta, Antonio M. Cabral. Role of intrarenal a2-adrenoceptors in the renal responses to xylazine in rats. Am J Physiol Regulatory Integrative Comp Physiol 278: R1074–R1081, 2000.—This study examined the contribution of intrarenal a2-adrenoceptor mechanisms to the enhanced urine flow rate (V) and urinary sodium excretion (UNaV) responses in ketaminexylazine-anesthetized rats. Ten minutes after left renal artery (LRA) injection, the a2-adrenoceptor antagonist yohimbine (5 μg) significantly decreased V from 58 6 8 to 35 6 7 μl ·min21 ·g kidney wt21 and UNaV from 2.8 6 0.4 to 2.1 6 0.4 μeq·min21 ·g kidney wt21 without altering right kidney function. The renal effects of the LRA injection of yohimbine were completely abolished in chronic bilaterally renal-denervated (RDNX) rats. In RDNX rats, a higher LRA dose of yohimbine (15 μg) significantly reduced left and right kidney V, with no effects on UNaV. In separate bladder-catheterized rats, yohimbine (0.5 mg/kg), 20 min after intravenous injection, significantly decreased V from 63 6 9 to 13 6 2 μl ·min21 ·g kidney wt21 and UNaV from 4.5 6 0.5 to 1.1 6 0.1 μeq·min21 ·g kidney wt21. In RDNX rats, this dose of yohimbine reduced V and UNaV, but the magnitude was blunted compared with intact rats. In contrast, 0.1 mg/kg iv yohimbine significantly reduced V and UNaV to similar magnitudes in intact and RDNX groups. Together, these findings indicate that intravenous xylazine acts by renal nerve-dependent and -independent mechanisms to enhance renal excretory function in ketamineanesthetized rats. Because the effects of the LRA dose of yohimbine were abolished in renal-denervated animals, it appears that xylazine has a direct renal action to augment the renal excretion of water and sodium via a presynaptic a2-adrenoceptor pathway that inhibits the release of neurotransmitters from renal sympathetic nerve terminals.