期刊
BRITISH JOURNAL OF PHARMACOLOGY
卷 131, 期 1, 页码 5-9出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bjp.0703537
关键词
hypoxic pulmonary vasoconstriction; Rho-associated kinases
We have examined the effects of Y-276321 a specific inhibitor of Rho-activated kinases (ROCK I and ROCK II) upon sustained hypoxic pulmonary vasoconstriction (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 concentration-dependent inhibition of acute sustained HPV in rat IPA. Application 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-dependent manner, resulting in complete ablation of the presser response to hypoxia at a concentration of 600 nM. Furthermore, addition of Y-27632 at any point during hypoxia caused a reversal of HPV in perfused rat lungs. These results suggest that activation of Rho-associated kinase may be a pivotal step in the generation of sustained HPV.
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