Inhibition of sustained hypoxic vasoconstriction by Y-27632 in isolated intrapulmonary arteries and perfused lung of the rat

We have examined the effects of Y-276321 a specific inhibitor of Rho-activa ted kinases (ROCK I and ROCK II) upon sustained hypoxic pulmonary vasoconst riction (HPV) in both rat isolated small intrapulmonary arteries (IPA) and perfused rat lungs in situ. Y-27632 (100 nM-3 mu M) was found to cause a co ncentration-dependent inhibition of acute sustained HPV in rat IPA. Applica tion of Y-27632 (10-600 nM) in perfused rat lungs caused no change in basal perfusion pressure, but was found to inhibit HPV in a concentration-depend ent manner, resulting in complete ablation of the presser response to hypox ia at a concentration of 600 nM. Furthermore, addition of Y-27632 at any po int during hypoxia caused a reversal of HPV in perfused rat lungs. These re sults suggest that activation of Rho-associated kinase may be a pivotal ste p in the generation of sustained HPV.