Effects of inhibition of nitric oxide formation on regional blood flow in experimental myocardial infarction.

Abstract

BACKGROUND Large myocardial infarction is associated with reactive hypertrophy and dilation of the left ventricle, depressed coronary flow reserve, and the development of heart failure including systemic vasoconstriction. We hypothetized that changes in endothelial function, e.g., in the synthesis or action of nitric oxide in the coronary and peripheral vasculatures, might be involved in the depressed coronary flow reserve and increased systemic vascular resistance observed in postinfarction myocardial hypertrophy and failure. METHODS AND RESULTS The regional blood flow changes that occur as a result of inhibiting the basal release of nitric oxide with NG-monomethyl-L-arginine (L-NMMA) and how this regional pattern may be altered in large MI (infarct size, 30-51% of left ventricle) were examined. Measurements were made 24 hours and 8 weeks after myocardial infarction or sham operation in conscious rats. The left ventricular end-diastolic pressure and effects of L-NMMA on left ventricular end-diastolic pressure was similar 24 hours and 8 weeks after myocardial infarction. The effects of L-NMMA (30 mg/kg i.v.) on heart rate and blood pressure were similar in infarcted and sham animals. L-NMMA exerted a marked vasoconstriction in the renal, splanchnic, cutaneous, and cerebral circulations of similar magnitude in sham-operated rats and animals with myocardial infarction. The coronary vasoconstrictor effect of L-NMMA was attenuated significantly in the hypertrophied right and noninfarcted left ventricle of 8-week-old infarcted rats (p less than 0.01 versus sham-operated animals) but not 24 hours after induction of myocardial infarction when cardiac hypertrophy has not yet developed. The increase in left ventricular coronary resistance in 8-week-old infarcted animals was inversely related to infarct size (r = -0.787, p = 0.012, n = 9). Nitroglycerin exerted similar increases in coronary blood flow in rats with chronic myocardial infarction and sham-operated animals, arguing against a reduced vascular responsiveness to nitric oxide. Transmission electron microscopy of coronary resistance vessels in 8-week-old infarcted animals did not reveal endothelial abnormalities. CONCLUSIONS These data suggest that the basal release of nitric oxide in the renal, intestinal, and cutaneous circulations is not affected adversely in this model of myocardial infarction and failure. However, the blunted coronary vasoconstrictor effect of L-NMMA late after large myocardial infarction supports the view that the basal release of nitric oxide is impaired in postinfarction reactive cardiac hypertrophy.