PULMONARY VASCULAR MUSCLE PROLIFERATION AS A RESULT OF PROTEIN AND mRNA-eNOS ALTERATIONS IN A RAT MODEL OF CHF

Endothelial Nitric Oxide Synthase (eNOS) produces nitric oxide (NO) from L-arginine and is important for the maintenance of cardiovascular homeostasis. Congestive heart failure (CHF) generally results in increased pulmonary blood flow and if untreated leads to pulmonary hypertension and end stage heart failure. We therefore hypothesized that increased pulmonary flow without changes in pressure would result in hypertrophy of the media (middle layer of vascular wall). NO produced by the lung is regulated by systemic blood flow and in turn adjusts smooth muscle proliferation via altered expression of eNOS. To study this hypothesis, we created an artificial aortocaval shunt in order to increase pulmonary flow for 7 weeks. The shunt resulted in a significant thickening of the media. eNOS Western and Northern blot analysis demonstrated no significant alterations of eNOS protein and mRNA levels in the large-shunted group but in the small shunted one in comparison with sham. We suggested that NO in low concentrations (about > 10µM) caused weak hypertrophy of the media in the small-shunted group and in high concentrations (about> 50µM) caused S-nitrosylation of eNOS protein and deamination of eNOS mRNA and the regulatory genes in the nucleus thus the media of the vascular wall was significantly thickened in the large-shunted group. In higher concentrations, NO induces apoptosis and decreased cell viability.