Abstract 2620: Chronic Nitric Oxide Inhibition Produces a Subpulmonary Stenosis and Right Ventricular Hypertrophy in the Absence of Pulmonary Hypertension
Nitric oxide (NO) is a major vasodilator and the inhibition of NO production has been shown to cause marked systemic hypertension and left heart hypertrophy. However, the precise role of NO in the modulation of pulmonary circulation remains controversial. We recently reported that increased endothelial NO production prevented pulmonary hypertension and right ventricular hypertrophy (RVH) in rats. However, an acute inhibition of pulmonary endothelial NO production failed to elicit an increase in pulmonary vascular resistance and pressure. To further investigate the importance of NO in the modulation of pulmonary circulatory system, we chronically treated rats with L-NAME, a specific NO synthase inhibitor, in drinking water (0.5 mg/ml). Three weeks after L-NAME treatment we found, as expected, a significant increase in aortic pressure and a marked hypertrophy of the LV and the ventricular septum. RV in these rats demonstrated a significantly increased intraventricular pressure with a slight hypertrophy. And surprisingly the pulmonary arterial pressure was not altered, suggesting a pressure gradient between the RV and the pulmonary circulation. Further echocardiographic examinations of these L-NAME treated rats revealed a slightly thickened RV wall, a turbulent RV flow pattern, a decreased RV ejection fraction, and a narrowed area in the right ventricular outflow tract. Histological examination subsequently identified that impediment of blood flow from RV to the pulmonary artery was due to a marked hypertrophy of the crista supraventricularis. This subpulmonary stenosis is a rare but clinically significant pulmonary disorder. Our findings suggest that chronic L-NAME treated rats provide an excellent animal model to further investigate the development of hypertrophic obstructive cardiomyopathy and its clinical management. In addition, the present chronic studies confirm our earlier acute studies and further demonstrate that control of pulmonary circulation is complex and that NO represents only one of the many local controls. The interaction between NO and other vascular mediators in the modulation of pulmonary circulation is currently under investigation.