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 x kg x (-1) x h(-1)), RNS reduced perfusion less (by -65 +/- 9% and -12 +/- 8% at 4 Hz) x alpha1-Adrenoceptor antagonism with prazosin (0.2 mg/kg plus 0.2 mg kg(-1)h(-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) x Y1 receptor- and alpha1-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 alpha1-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 alpha1-adrenoceptor-mediated neurotransmission in the control of renal perfusion.

ANG II type 2 receptors and neural control of intrarenal blood flow

“…As we have found previously (16,17,21,34,35), responses to RNS were highly reproducible across the course of the experiment in control rabbits (group 1). By analyzing our results mainly in a within-animal fashion, we were able to detect relatively modest effects of ANG II and PD123319 on responses to RNS, even though responses to RNS can vary somewhat in different rabbits.…”

“…kidney medulla; renal circulation; renin-angiotensin system; sympathetic nervous system THE RENAL MEDULLARY MICROCIRCULATION (7)(8)(9)(10)20), the renal sympathetic nerves (11), and the renin-angiotensin system (37) all play key roles in long-term regulation of arterial pressure. Renal sympathetic nerves innervate juxtamedullary afferent and efferent arterioles and outer medullary descending vasa recta (17,18), vascular elements likely important in control of medullary perfusion (20). Angiotensin type 2 (AT 2 ) and/or AT 1 receptors are also localized to these vascular elements (32).…”

Sympathetic nerve-derived ATP regulates renal medullary vasa recta diameter via pericyte cells: a role for regulating medullary blood flow?

“…In accordance with the functional data describing a key role for sympathetic nerve-derived ATP in the regulation of vasa recta diameter via contractile pericytes, we have previously reported that vasa recta and associated pericytes express mRNA for P2X1, 3, and 7 and P2Y4 and 6 (Crawford et al, 2011). Interestingly, in vivo studies in rabbits conclude that P2X receptors do not contribute to neurally mediated vasoconstriction (Eppel et al, 2006a,b,c), however this is perhaps not surprising given that we have previously demonstrated much higher levels (40-fold) of P2Y (P2Y 4 and P2Y 6 ) than P2X receptor mRNA in rat isolated vasa recta, with pericytes in situ (Crawford et al, 2011); supporting sympathetically-derived ATP acting via P2Y receptors on pericytes to mediate vasoconstriction of vasa recta.…”

“…Tyramine-evoked vasoconstriction of vasa recta by pericytes was significantly inhibited (~50%) by the P2 receptor antagonist suramin (Figure 2C), suggesting a key role for sympathetic purinergic signaling in the regulation of MBF by renal pericytes. Interestingly, others have shown that the α-adrenoceptor antagonist prazosin greatly reduces RBF and CBF in response to renal nerve stimulation, yet MBF was both reduced and increased (Chapman et al, 1982; Eppel et al, 2004, 2006a,b,c). This may of course be due to the relative expression of α-adrenoceptors in the vasculature throughout the kidney, which was not reported by authors of these studies.…”

Lack of contribution of P2X receptors to neurally mediated vasoconstriction in the rabbit kidney in vivo

“…However, most of our knowledge of the effects of P2X‐receptor activation on renal vascular tone comes from in vitro models. Our recent studies investigating the renal responses to RNS in the rabbit in vivo suggest that non‐adrenergic neurotransmitters, such as neuropeptide Y, may be important mediators of neurally induced vasoconstriction (Eppel et al 2006). To test the hypothesis that P2X‐receptor activation by ATP contributes to neurally mediated vasoconstriction in the rabbit kidney in vivo , we tested responses to RNS before and during renal arterial infusion of α , β ‐mATP.…”