RESUMEN
BACKGROUND: The present study was aimed (1) to assess the effects of nitric oxide (NO) synthesis inhibitor on regional myocardial function and systemic and pulmonary hemodynamics; (2) to determine whether the blockade of the cyclo-oxygenase (COX) pathway modifies these effects on the variables, and (3) to investigate the mechanism of cardiac depression following NO synthesis inhibition in an open-chest canine model. METHODS: Twenty-five dogs of either sex were acutely instrumented under 1.6% ethrane anesthesia to measure aortic, pulmonary arterial and left ventricular pressure, pulmonary (cardiac output) and left circumflex coronary flow, and subendocardial segment length. NG-nitro-L-arginine methyl ester (L- NAME) at doses of 0.3, 1.0, 3.0, or 10.0 mg/kg i.v. was administered alone (control dogs, n = 10) or in the presence of COX inhibitor, indomethacin (10 mg/kg i.v., n = 10). Seven dogs (n = 7) received phenylephrine at doses of 0.1, 0.3, 1.0, or 3.0 microgram/kg/min i.v. to compare its hemodynamic effects with those of L-NAME. The preload recruitable stroke work slope (Mw) and percent systolic shortening (%SS) as an index of regional myocardial contractility, and the maximum segment lengthening rate (dL/dt max) and percent post-systolic shortening (%PSS) as an index of regional diastolic function, were evaluated. RESULTS: L-NAME dose-dependantly attenuated both regional systolic (Mw and %SS) and diastolic functions (dL/dt max and %PSS), whereas it caused an increase of coronary flow. L-NAME dose- dependently increased systemic blood pressure and vascular resistance as well as pulmonary arterial pressure and vascular resistance. L-NAME also reduced cardiac and stroke volume indices. Pretreatment with indomethacin did not affect the regional myocardial and systemic hemodynamic responses to L-NAME, but did blunt the coronary flow and pulmonary pressure responses. The magnitude of decreases in cardiac and stroke volume indices and Mw was greater with L-NAME than with phenylephrine (P <0.05), despite the comparable blood pressure increases. CONCLUSIONS:These results suggest (1) that NO plays a significant role in cardiac function as well as in systemic and pulmonary but not coronary, vasomotor activities, and (2) that COX products are involved in pulmonary hemodynamic responses to NO synthesis inhibition. It is also suggested that the decline in cardiac output following the NO synthesis inhibition results from a direct myocardial depressant effect of the drug.