Rho kinase is involved in Ca entry of rat penile small arteries

Villalba N, Stankevicius E, Simonsen U, Prieto D. Rho kinase is involved in Ca entry of rat penile small arteries. Am J Physiol Heart Circ Physiol 294: H1923–H1932, 2008. First published January 25, 2008; doi:10.1152/ajpheart.01221.2007.—Tonic physiological activity of RhoA/Rho kinase contributes to the maintenance of penile flaccidity through its involvement in the Ca sensitization of erectile tissue smooth muscle. The present study hypothesized that Rho kinase is also involved in the modulation of Ca entry induced by 1adrenoceptor stimulation of penile arteries. Rat penile arteries were mounted in microvascular myographs for simultaneous measurements of intracellular Ca ([Ca ]i) and force. The Rho-kinase inhibitor Y-27632 markedly reduced norepinephrine-mediated electrically induced contractions and the increases in both [Ca ]i and tension elicited by the 1-adrenoceptor agonist phenylephrine (Phe). In contrast, the protein kinase C (PKC) inhibitor Ro-31-8220 reduced tension without altering the Phe-induced increase in [Ca ]i. In the presence of nifedipine, Y-27632 still inhibited the non-L-type Ca signal and blunted Phe contraction. Y-27632 did not impair the capacitative Ca entry evoked by store depletion with cyclopiazonic acid but largely reduced the Ba influx stimulated by Phe in fura-2 AM-loaded arteries. The addition of Y-27632 to arteries depolarized with high KCl markedly reduced tension without changing [Ca ]i. In -toxin-permeabilized penile arteries stimulated with threshold Ca concentrations, Y-27632 inhibited the sensitization induced by either guanosine 5 -O-(3-thiotriphosphate) (GTP S) or Phe in the presence of GTP S. However, Y-27632 failed to alter contractions induced by a maximal concentration of free Ca . These results suggest that Rho kinase, besides its contribution to the Ca sensitization of the contractile proteins, is also involved in the regulation of Ca entry through a nonselective cation channel activated by 1-adenoceptor stimulation in rat penile arteries.