Role of rho-kinase in the regulation of vascular tone in hypertensive renal transplant recipients

Activation of rho-kinase (ROK) is involved in the development of hypertension as it is a potent regulator of vascular smooth muscle cell (VSMC) contractility. Here we evaluated whether activation of ROK is present in hypertensive kidney transplant recipients (NTX).We tested the effect of the ROK-inhibitor fasudil on the regulation of forearm blood flow (FBF) in NTX and in healthy control subjects (CTL). In addition potential modulating effects of ROK-inhibition on local vascular nitric oxide (NO) release were studied.The effect of intra-arterial infusion of fasudil on FBF was studied by venous-occlusion plethysmography in NTX and CTL. To unmask the role of NO fasudil was infused with/without clamping of vascular NO in NTX and CTL. To unravel the basal NO-mediated tone the NO-synthase inhibitor l-NMMA was infused.Fasudil markedly but comparably increased FBF in NTX and CTL. The vascular response to fasudil was blunted during NO-clamp in CTL (104 ± 18% vs. 244 ± 48% for NO-clamp + fasudil vs. fasudil alone; baseline = 0%, P < 0.05) but not in NTX. The l-NMMA-induced vasoconstriction was impaired in NTX compared to CTL.In NTX and CTL basal vascular tone equally depends on ROK. Fasudil-induced vasodilatation is partly mediated by vascular NO in CTL but not in NTX. The greater NO-insensitive fasudil-induced increase in FBF in NTX suggests an increased ROK-mediated VSMC constrictor tone in these patients. Basal NO-mediated tone is attenuated in hypertensive NTX.