Abstract
Data on the role of nitric oxide (NO) in monocrotaline (MC)-induced pulmonary hypertension of rats have all been derived from in vitro measurements. In vivo pulmonary hemodynamics and microvascular responses to NO blockade in MC-treated rats have not been reported. The current study evaluated the role of NO in live MC-treated rats. Male Sprague-Dawley rats (n = 29) were divided into saline control and MC-treated groups. Three to 4 weeks after either saline or MC injection, pulmonary hemodynamics were measured using pulmonary arterial catheter and thermodilution techniques. Pulmonary microvascular diameter changes were assessed using an intravital microscope. Three to 4 weeks after subcutaneous injection of MC (50 mg/kg), MC-treated rats showed elevated pulmonary arterial pressure compared to control rats (23.6 +/- 2.9 mm Hg vs 14.5 +/- 0.8 mm Hg). N(omega)-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg, intravenously), an NO synthase inhibitor, produced significant increases in pulmonary arterial pressure and total pulmonary vascular resistance compared to control rats (12.3 +/- 2.5 mm Hg vs 1.0 +/- 0.9 mm Hg; 0.21 +/- 0.04 mm Hg/mL/min vs 0.05 +/- 0.02 mm Hg/mL/min, p < 0.05). Intravital microscopic observation of the subpleural vessels showed significant vasoconstriction in medium-sized (> 40 microm) pulmonary arterioles of MC-treated rats following L-NAME administration (58.4 +/- 3.6 microm vs 47.1 +/- 3.4 microm, p < 0.05) while no significant diameter changes were found in either the small-sized (< 40 microm) pulmonary arterioles or pulmonary venules. Diameters of pulmonary arterioles and venules in control rats were not affected by L-NAME administration. Pulmonary arterial pressure and pulmonary vascular resistance increased after NO blockade in live MC-treated rats. The site of vasoconstriction after NO blockade included medium-sized pulmonary arterioles but not small-sized pulmonary arterioles. This study has provided both macro- and microhemodynamic evidence of a modulatory role of NO in live MC-treated rats.
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