Nitric oxide impacts on angiotensin AT2 receptors modulation of high‐pressure baroreflex control of renal sympathetic nerve activity in rats

Abstract

To investigate the interaction of NO with AT2 receptor activation in the modulation of high‐pressure baroreceptor regulation of renal sympathetic nerve activity (RSNA). Experiments were carried out in chloralose/urethane anaesthetised rats and baroreflex gain curves were generated using intravenous phenylephrine and sodium nitroprusside following intracerebroventricular (I.C.V.) saline, CGP42112 (CGP), PD123319 (PD), AT2 receptor agonist and antagonist, and then in combination with L‐NAME, an NO synthase inhibitor. I.C.V. saline, PD and CGP did not change baseline mean arterial pressure (MAP), heart rate (HR) or RSNA (86±3 vs. 85±3 mmHg, 328±11 vs. 326±10 beat/min, 0.79±0.15 vs. 0.75±0.14 μV.s, respectively). The slope of the baroreflex gain curve for RSNA was increased by 64% and 107% following L‐NAME and CGP respectively but decreased by 19% following PD (all P<0.05). In the group where PD preceded L‐NAME or when PD followed L‐NAME, the slope of the baroreflex gain curve during PD plus L‐NAME infusion was reduced by about 35% (P<0.05) compared to the infusion of PD or L‐NAME alone. L‐NAME decreased the slope of the baroreflex gain curve following CGP I.C.V. administration by 33% (P<0.05). These findings suggest that NO exerts a facilitatory action allowing the normal high‐pressure baroreceptor reflex regulation of RSNA mediated through central AT2 receptor activation.Funded by the Wellcome Trust