The effects of cyclooxygenase and nitric oxide synthase inhibition on cardiodynamic parameters and coronary flow in isolated rat hearts.

Abstract

Background: Despite the widespread clinical use of cyclooxygenase (COX) inhibitors, dilemmas regarding the potential impact of these drugs on the cardiovascular system persist.

Objective: To estimate the effects of different COX inhibitors (meloxicam, acetylsalicylic acid [ASA] and SC-560) on cardiac function and coronary flow in isolated rat hearts, with special focus on the L-arginine/nitric oxide system.

Methods: The hearts of eight-week-old male Wistar albino rats (n=72; 12 rats per group; body mass 180 g to 200 g) were retrogradely perfused according to the Langendorff technique at gradually increased perfusion pressure (40 cmH2O to 120 cmH2O). After control experiments, the hearts were perfused with the following drugs: 100 μM ASA, alone or in combination with 30 μM N(ω)-nitro-L-arginine monomethyl ester (L-NAME), 0.3 μM meloxicam with or without 30 μM L-NAME, 3 μM meloxicam with or without 30 μM L-NAME, 30 μM L-NAME and 0.25 μM SC-560. In the control and experimental groups, the following parameters of heart function were continuously recorded: maximum rate of left ventricular pressure development, minimum rate of left ventricular pressure development, systolic left ventricular pressure, diastolic left ventricular pressure, heart rate and mean blood pressure. Coronary flow was measured flowmetrically. The amount of released NO2 (-) was determined spectrophotometrically in coronary venous effluent.

Results: While meloxicam and SC-560 were found to have an adverse influence on cardiac function and coronary perfusion, ASA did not negatively affect the intact model of the heart.

Conclusion: It appeared that interaction between COX and the L-arginine/nitric oxide system truly exists in coronary circulation and may explain the causes of the observed effects.