Effects of Protein Kinase C on Hypoxic Pulmonary Vasoconstriction in Isolated Rat Lungs / 대한마취과학회지

ABSTRACT

BACKGROUND: Protein kinase C represents an important component of a signal transduction pathway that regulates vascular smooth muscle contraction. This study was performed with an inhibitor and activators of protein kinase C to determine their effects on hypoxic pulmonary vasoconstriction (HPV) in isolated rat lung model. METHODS: Isolated lungs from Sprague-Dawley rats were ventilated with a normoxic gas (21%O2-5%CO2-balanced N2) and a hypoxic gas (3%O2-5%CO2-balanced N2) alternatively, and then perfused with constant pulmonary blood flow. Baseline hypoxic pressor responses (delta PAP) were measured as the difference of pulmonary artery pressure between normoxic ventilation and hypoxic ventilation. After baseline delta PAP had obtained, rats were randomly divided into a chelerythrine group, an phorbol 12, 13-dibutyrate (PDBu) group, and a farnesylthiotriazole (FTT) group. The different concentrations of each drug were added into the perfusate sequentially. delta PAP in the different concentrations of each drug were calculated as a percentage of the delta PAP in each concentration of drug to the baseline delta PAP in the absence of drug (%delta PAP). RESULTS: The %delta PAP of chelerythrine were 83.7 +/- 19.2%, 71.5 +/- 24.1% and 68.4 +/- 28.3% at 0.1, 1, and 10micrometer, respectively (P < 0.05). The %delta PAP of PDBu were 111.3 +/- 10.1%, 144.4 +/- 37.8% and 168.4 +/- 89.1% at 20, 100, and 300 nM, respectively (P < 0.05). The %delta PAP of FTT were 80.1 +/- 25.1%, 61.0 +/- 17.2% and 30.1 +/- 18.4% at 1, 10, and 30micrometer, respectively (P < 0.05). CONCLUSIONS: The results of this study suggest that regulator of protein kinase C influence HPV.