Rho kinase inhibitors reduce neurally evoked contraction of the rat tail artery in vitro

The effects of Rho kinase inhibitors (Y27632, HA‐1077) on contractions to electrical stimulation and to application of phenylephrine, clonidine or α,β ‐methylene adenosine 5′‐triphosphate ( α,β ‐mATP) were investigated in rat tail artery in vitro . In addition, continuous amperometry and intracellular recording were used to monitor the effects of Y27632 on noradrenaline (NA) release and postjunctional electrical activity, respectively. Y27632 (0.5 and 1  μ M ) and HA‐1077 (5  μ M ) reduced neurally evoked contractions. In contrast, the protein kinase C inhibitor, Ro31‐8220 (1  μ M ), had little effect on neurally evoked contraction. In the absence and the presence of Y27632 (0.5  μ M ), the reduction of neurally evoked contraction produced by the α ‐adrenoceptor antagonists prazosin (10 n M ) and idazoxan (0.1  μ M ) was similar. The P2‐purinoceptor antagonist, suramin (0.1 m M ), had no inhibitory effect on neurally evoked contraction in the absence or the presence of Y27632 (1  μ M ). In the presence of Y27632, desensitization of P2X‐purinoceptors with α,β ‐mATP (10  μ M ) increased neurally evoked contractions. Y27632 (1  μ M ) and H‐1077 (5  μ M ) reduced sensitivity to phenylephrine and clonidine. In addition, Y27632 reduced contractions to α,β ‐mATP (10  μ M ). Y27632 (1  μ M ) had no effect on the NA‐induced oxidation currents or the purinergic excitatory junction potentials and NA‐induced slow depolarizations evoked by electrical stimulation. Rho kinase inhibitors reduce sympathetic nerve‐mediated contractions of the tail artery. This effect is mediated at a postjunctional site, most likely by inhibition of Rho kinase‐mediated ‘Ca 2+ sensitization’ of the contractile apparatus.British Journal of Pharmacology (2005) 146 , 854–861. doi: 10.1038/sj.bjp.0706377