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

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%-5%C-balanced ) and a hypoxic gas (3%-5%C-balanced ) alternatively, and then perfused with constant pulmonary blood flow. Baseline hypoxic pressor responses (PAP) were measured as the difference of pulmonary artery pressure between normoxic ventilation and hypoxic ventilation. After baseline 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. PAP in the different concentrations of each drug were calculated as a percentage of the PAP in each concentration of drug to the baseline PAP in the absence of drug (%PAP). Results: The %PAP of chelerythrine were 83.7 19.2%, 71.5 24.1% and 68.4 28.3% at 0.1, 1, and 10M, respectively (P 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 PAP of FTT were 80.1 25.1%, 61.0 17.2% and 30.1 18.4% at 1, 10, and 30M, respectively (P