The effects of modulation of endothelial derived nitric oxide level on contractile function and myocardial oxygen consumption in saline perfused mouse heart

Abstract

The aim of the study was to estimate myocardial oxygen consumption during modulation of nitric oxide levels by stimulating or inhibiting endogenous nitric oxide synthesis and by applying nitric oxide exogenously. Isolated mouse hearts (n=97) were paced and perfused at constant flow (16.0 ± 0.3 ml*g-1*min-1). Basal contractility and myocardial oxygen consumption were 2.30 ± 0.02 mmHg*ms-1 and 10.7 _ 0.2 _mol*g-1*min-1, respectively. Maximal stimulation of nitric oxide formation by bradykinin (10 _mol*l-1) increased coronary venous nitrite release 5-fold to 960 pmol*g-1*min-1 (n=17). Vasodilatation, induced by either bradykinin or adenosine caused a fall in perfusion pressure and a distinct decrease in contractility and myocardial oxygen consumption. Therefore, all further experiments were conducted at the maximal vasodilatation (adenosine, 1 _mol*l-1). Under these conditions, no effect of bradykinin on contractility and oxygen consumption rate was seen. Also, authentic nitric oxide in concentrations less than 2 _mol*l-1 did not alter either contractility or myocardial oxygen consumption. Only concentrations of nitric oxide higher than 5 _mol*l-1 induced contractile dysfunction and reduction in myocardial oxygen consumption. Finally inhibition of nitric oxide synthase had only marginal effects (n=6). Thus in the saline perfused mouse heart, neither the basal release of nitric oxide nor the bradykinin induced stimulation of endothelial nitric oxide formation are quantitatively sufficient to impair myocardial oxygen consumption.