Type 1 neuropeptide Y receptors and α1-adrenoceptors in the neural control of regional renal perfusion

Abstract

The aim of this study was to determine the contribution of neuropeptide Y (NPY) Y1 receptors in neurally mediated reductions in renal medullary perfusion. In pentobarbital sodium-anesthetized rabbits, electrical stimulation of the renal nerves (RNS, 0.5–16 Hz) decreased renal perfusion in a frequency-dependent manner. Under control conditions, 4 Hz reduced cortical and medullary perfusion by −85 ± 3% and −43 ± 7%, whereas 8 Hz reduced them by −93 ± 2% and −73 ± 4%, respectively. After Y1 receptor antagonism with BIBO3304TF (0.1 mg/kg plus 0.2 mg·kg·−1·h−1), RNS reduced perfusion less (by −65 ± 9% and −12 ± 8% at 4 Hz). α1-Adrenoceptor antagonism with prazosin (0.2 mg/kg plus 0.2 mg kg−1h−1) also inhibited RNS-induced reductions in renal perfusion (−80 ± 4% and −37 ± 10% reductions in the cortex and medulla, respectively, at 8 Hz). When given after BIBO3304TF treatment, prazosin inhibited RNS-induced reductions in cortical and medullary perfusion more profoundly (−57 ± 12% and −25 ± 9% reductions, respectively, at 8 Hz). Y1 receptor- and α1-adrenoceptor-blockade were confirmed by testing vascular responses to renal arterial NPY and phenylephrine boluses. NPY-positive immunolabeling was observed around interlobular arteries, afferent and efferent arterioles, and in the outer medulla. In conclusion, Y1 receptors and α1-adrenoceptors contribute to RNS-induced vasoconstriction in the vessels that control both cortical and medullary perfusion. Consistent with this, NPY immunostaining was associated with blood vessels that control perfusion in both regions. There also seems to be an interaction between Y1 receptors and α1-adrenoceptor-mediated neurotransmission in the control of renal perfusion.