Rho kinase is involved in Ca2+ entry of rat penile small arteries.
Tonic physiological activity of RhoA/Rho kinase contributes to the maintenance of penile flaccidity through its involvement in the Ca(2+) sensitization of erectile tissue smooth muscle. The present study hypothesized that Rho kinase is also involved in the modulation of Ca(2+) entry induced by alpha(1)-adrenoceptor stimulation of penile arteries. Rat penile arteries were mounted in microvascular myographs for simultaneous measurements of intracellular Ca(2+) ([Ca(2+)](i)) and force. The Rho-kinase inhibitor Y-27632 markedly reduced norepinephrine-mediated electrically induced contractions and the increases in both [Ca(2+)](i) and tension elicited by the alpha(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(2+)](i). In the presence of nifedipine, Y-27632 still inhibited the non-L-type Ca(2+) signal and blunted Phe contraction. Y-27632 did not impair the capacitative Ca(2+) entry evoked by store depletion with cyclopiazonic acid but largely reduced the Ba(2+) 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(2+)](i). In alpha-toxin-permeabilized penile arteries stimulated with threshold Ca(2+) concentrations, Y-27632 inhibited the sensitization induced by either guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) or Phe in the presence of GTPgammaS. However, Y-27632 failed to alter contractions induced by a maximal concentration of free Ca(2+). These results suggest that Rho kinase, besides its contribution to the Ca(2+) sensitization of the contractile proteins, is also involved in the regulation of Ca(2+) entry through a nonselective cation channel activated by alpha(1)-adenoceptor stimulation in rat penile arteries.
Villalba
Nuria
N
Dept. de Fisiología, Facultad de Farmacia, Univ. Complutense, 28040-Madrid, Spain.
Stankevicius
Edgaras
E
Simonsen
Ulf
U
Prieto
Dolores
D
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000378:metabolism; D001427:Bacterial Toxins / Q000494:pharmacology; D001464:Barium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D010413:Penis / Q000098:blood supply*; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000577:Amides; D001427:Bacterial Toxins; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D018340:Receptors, Adrenergic, alpha-1; D014662:Vasoconstrictor Agents; C108830:Y 27632; D010656:Phenylephrine; D001464:Barium; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D011189:Potassium Chloride; D054460:rho-Associated Kinases; D011493:Protein Kinase C; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D009543:Nifedipine; D002118:Calcium; C064758:Ro 31-8220; D009638:Norepinephrine; C000543:cyclopiazonic acid