Hypoxic pulmonary vasoconstriction and pulmonary artery tissue cytokine expression are mediated by protein kinase C

Background. Pulmonary arteries exhibit a marked vasoconstriction when exposed to hypoxic conditions. Although this may be an adaptive response to match lung ventilation with perfusion, the potential consequences of sustained pulmonary vasoconstriction include pulmonary hypertension and right heart failure. The concomitant production of proinflammatory mediators by the pulmonary artery itself may exacerbate acute increases in pulmonary vascular resistance. We hypothesized that acute hypoxia causes pulmonary arterial contraction and increases the pulmonary artery tissue expression of proinflammatory cytokines via a protein kinase C (PKC) mediated mechanism. Methods. Isometric force displacement was measured in isolated rat pulmonary artery rings during hypoxia (95% N2/5% CO2, pO2 = 30–35 mmHg) in the presence and absence of the protein kinase C inhibitor chelerythrine (1 μmol/L). Following 60 min of hypoxia, pulmonary artery rings were subjected to mRNA analysis for TNF-μ, IL-1β, and iNOS via RT-PCR. Data were analyzed using two-way analysis of variance (ANOVA) with post-hoc Bonferonni test or unpaired t tests with alpha level less than 0.05 considered statistically significant. Results. Hypoxia caused a biphasic contraction: an early and delayed contraction which occurred 1–3 and 15–20 min, respectively, after the onset of hypoxia. Hypoxic pulmonary artery tissue had increased expression of TNF-μ, IL-1β, and iNOS mRNA compared to normoxic controls. PKC inhibition significantly (P