Central Angiotensin-II Increases Renal Sympathetic Nerve Activity Via Rho Kinase Activation in Conscious Rabbits

BackgroundA growing body of evidence implicates elevated renal sympathetic tone and activation of the renin-angiotensin system in the pathogenesis and progression of cardiovascular disease. The RhoA/Rho kinase pathway is an important mediator of the effects of Angiotensin-II (AngII) in the periphery, but the functional role of this pathway in AngII-induced renal sympatho-excitation is not well-characterized. HypothesisWe hypothesized that central inhibition of the RhoA/Rho kinase pathway prevents AngII-mediated renal sympatho-excitation. MethodsSixteen male New Zealand White rabbits were chronically instrumented with renal sympathetic nerve electrodes, arterial pressure telemetries, and lateral ventricle cannulae. Each rabbit received an intracerebroventricular infusion of AngII, the Rho kinase inhibitor Fasudil (Fas), AngII and Fas, or a vehicle infusion. Seven days after renal nerve electrode implantation, baseline renal sympathetic nerve activity was recorded and quantified by normalization to the naso...