tailieunhanh - Báo cáo y học: " Diacylglycerol regulates acute hypoxic pulmonary vasoconstriction via TRPC6"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học 'Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài:" Diacylglycerol regulates acute hypoxic pulmonary vasoconstriction via TRPC6. | Fuchs et al. Respiratory Research 2011 12 20 http content 12 1 20 RESPIRATORY RESEARCH RESEARCH Open Access Diacylglycerol regulates acute hypoxic pulmonary vasoconstriction via TRPC6 Beate Fuchs1 Markus Rupp1 Hossein A Ghofrani1 Ralph T Schermuly1 2 Werner Seeger1 2 Friedrich Grimminger3 Thomas Gudermann4 Alexander Dietrich4 Norbert Weissmann1 Abstract Background Hypoxic pulmonary vasoconstriction HPV is an essential mechanism of the lung that matches blood perfusion to alveolar ventilation to optimize gas exchange. Recently we have demonstrated that acute but not sustained HPV is critically dependent on the classical transient receptor potential 6 TRPC6 channel. However the mechanism of TRPC6 activation during acute HPV remains elusive. We hypothesize that a diacylglycerol DAG -dependent activation of TRPC6 regulates acute HPV. Methods We investigated the effect of the DAG analog 1-oleoyl-2-acetyl-sn-glycerol OAG on normoxic vascular tone in isolated perfused and ventilated mouse lungs from TRPC6-deficient and wild-type mice. Moreover the effects of OAG the DAG kinase inhibitor R59949 and the phospholipase C inhibitor U73122 on the strength of HPV were investigated compared to those on non-hypoxia-induced vasoconstriction elicited by the thromboxane mimeticum U46619. Results OAG increased normoxic vascular tone in lungs from wild-type mice but not in lungs from TRPC6-deficient mice. Under conditions of repetitive hypoxic ventilation OAG as well as R59949 dose-dependently attenuated the strength of acute HPV whereas U46619-induced vasoconstrictions were not reduced. Like OAG R59949 mimicked HPV since it induced a dose-dependent vasoconstriction during normoxic ventilation. In contrast U73122 a blocker of DAG synthesis inhibited acute HPV whereas U73343 the inactive form of U73122 had no effect on HPV. Conclusion These findings support the conclusion that the TRPC6-dependency of acute HPV is induced via DAG. Introduction Hypoxic pulmonary .