Nifedipine inhibits hypoxia induced transvascular leakage through down regulation of NFkB.

Abstract

We have studied the prophylactic administration of nifedipine and its molecular mechanism involved in reducing the transvascular leakage and inflammation in rats under hypoxia. Rats exposed to an altitude of 7620m for 6h resulted into significant increase in transvascular leakage, oxidative stress with increased NFkB expression in lungs followed by significant increase in pro inflammatory cytokines (IL-1, TNF-α) with up regulation of cell adhesion molecules (ICAM-I, VCAM-I, E-selectin, and P-selectin) in the lungs over control. Prophylactic administration of nifedipine significantly reduced the transvascular leakage, oxidative stress, inhibited the up regulation of NFkB in lungs of rats compared to control. In addition, nifedipine significantly suppressed the levels of proinflammatory cytokines and cell adhesion molecules and stabilized the HIF1-α accumulation in the lungs of rats compared to control. These results indicate that, nifedipine has an inhibitory effect on initial leaking and showed reduction in progression of inflammation through down regulation of NFkB activity in lungs of rats under hypoxia.