Effect of changes in pH on wall tension in isolated rat pulmonary artery: role of the XXXX /Rho-kinase pathway.

@entity2426 @entity12223 @entity520 @entity2647 @entity594 @entity141 @entity20757 @entity2472
Pulmonary arteries (PA) are resistant to the vasodilator effects of extracellular @entity520 in systemic vessels; the mechanism underlying this difference between systemic and pulmonary circulations has not been elucidated. We hypothesized that @entity20757 /Rho-kinase-mediated @entity141 sensitization pathway played a greater role in tension development in pulmonary than in systemic vascular smooth muscle and that this pathway was insensitive to @entity520 . In arterial rings contracted with the alpha1-agonist @entity2647 (PE), the Rho-kinase inhibitor @entity12223 (< or =3 microM) induced greater relaxation in precontracted PA rings than in aortic rings. In PA rings stimulated by PE, the activation of @entity20757 was greater than in aorta. @entity520 ( @entity520 ) induced a smaller relaxation in precontracted PA than in aorta. However, in the presence of @entity594 and @entity2426 , when PE-induced @entity2472 was predominantly mediated by Rho-kinase, the relaxant effect of @entity520 was reduced and similar in both vessel types. Furthermore, in the presence of @entity12223 , @entity520 induced a greater relaxation in both PA and aorta, which was similar in both vessels. Finally, in alpha-toxin-permeabilized smooth muscle, PE-induced @entity2472 at constant @entity141 activity was inhibited by @entity12223 and unaffected by @entity520 . These results indicate that @entity141 sensitization induced by the @entity20757 /Rho-kinase pathway played a greater role in agonist-induced vascular smooth muscle @entity2472 in PA than in aorta and that tension mediated by this pathway was insensitive to @entity520 . The predominant role of the @entity20757 /Rho-kinase pathway in the pulmonary vasculature may account for the resistance of this circulation to the vasodilator effect of @entity520 observed in the systemic circulation.
