Chronic hypoxia decreases arterial and venous compliance in isolated perfused rat lungs: an effect that is reversed by exogenous <scp>l</scp>-arginine
Chronic hypoxia (CH)-induced pulmonary hypertension is characterized by vasoconstriction and vascular remodeling, leading to right ventricular dysfunction. Given the role of arterial compliance ( C a ) in right ventricular work, a decrease in C a would add to right ventricular work. Nitric oxide (NO) is a potent vasodilator made by NO synthases from l-arginine (l-Arg). However, little is known of the effect of l-Arg on vascular compliance ( C v ) in the lung. We hypothesized that exposure to CH would decrease C a and that this effect would be reversed by exogenous l-Arg. Sprague-Dawley rats were exposed to either normoxia or CH for 14 days; the lungs were then isolated and perfused. Vascular occlusions were performed and modeled using a three-compliance, two-resistor model. Pressure-flow curves were generated, and a distensible vessel model was used to estimate distensibility and a vascular resistance parameter ( R 0 ). Hypoxia resulted in the expected increase in arterial resistance ( R a ) as well as a decrease in both C a and C v . l-Arg had little effect on R a , C a , or C v in isolated lungs from normoxic animals. l-Arg decreased R a in lungs from CH rats and redistributed compliance to approximately that found in normoxic lungs. CH increased R 0 , and l-Arg reversed this increase in R 0 . l-Arg increased exhaled NO, and inhibition of l-Arg uptake attenuated the l-Arg-induced increase in exhaled NO. These data demonstrate that the CH-induced decrease in C a was reversed by l-Arg, suggesting that l-Arg may improve CH-induced right ventricular dysfunction.