Role of intrarenal α2-adrenoceptors in the renal responses to xylazine in rats

Abstract

This study examined the contribution of intrarenal α2-adrenoceptor mechanisms to the enhanced urine flow rate (V) and urinary sodium excretion (UNaV) responses in ketamine-xylazine-anesthetized rats. Ten minutes after left renal artery (LRA) injection, the α2-adrenoceptor antagonist yohimbine (5 μg) significantly decreased V from 58 ± 8 to 35 ± 7 μl ⋅ min− 1 ⋅ g kidney wt− 1 and UNaV from 2.8 ± 0.4 to 2.1 ± 0.4 μeq ⋅ 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 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 ± 9 to 13 ± 2 μl ⋅ min− 1 ⋅ g kidney wt− 1 and UNaV from 4.5 ± 0.5 to 1.1 ± 0.1 μeq ⋅ min− 1 ⋅ g kidney wt− 1. 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 ketamine-anesthetized 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 α2-adrenoceptor pathway that inhibits the release of neurotransmitters from renal sympathetic nerve terminals.