744-3 Inhibition of Nitric Oxide Synthesis does not Increase Cardiac Contractile Response but Reduces Coronary Blood Flow Response to β-Adrenergic Stimulation in Normal Dogs

Although the induction of nitric oxide (NO) synthesis has been implicated as a cause of cytokine-induced depression of cardiac β-adrenergic responsiveness. whether the NO system constitutively present in the normal myocardium plays a role in its physiologic response to β-adrenergic stimulation in vivoremains controversial. Accordingly, we examined the effects of low and high doses of NW-nitro-L-arginine methyl ester (L-NAME)(10 and 100 μg/kg/min for 10 min), an NO synthase inhibitor, administered into left circumflex coronary artery (LCX) on responses of peak left ventricular (LV) dP/dt, regional wall thickening in LCX region and LCX blood flow to graded intracoronary (IC) doses of isoproterenol (ISO:0.002 to 0.016 μg/kg/min) in 7 anesthetized dogs. IC L-NAME was associated with dose-related reductions in IC acetylcholine-induced coronary vasodilation. Effects of L-NAME on ISO-induced changes are shown:baselineISO:0.0020.0040.008.0016Peak LV dP/dt (mmHg/sec) (n=7)control2029±1362586±1922820±2003309±2554120±419*low L-NAME2171±1492566±1762894±2063214±2233707±250*high L-NAME2114±1662326±1932560±1523014±1403354±171*Wall thickening (%) (n=2)control22±725±629±533±735±9low L-NAME25±1125±1528±1931±1836±21high L-NAME28±1725±1525±1531±1934±15LCX blood flow (ml/min)(n=7)control33±648±752±661±870±9*low L-NAME36±741±844±947±852±9*high L-NAME33±736±838±740±748±8*mean ± SEM*p<0.05Thus, inhibition of NO synthesis by L-NAME did not change baseline contractility nor did it increase its response to ISO. It also did not alter baseline blood flow, but reduced significantly its response to ISO. These data strongly suggest that the NO system in the normal myocardium does not modulate contractility, but NO formation in the vasculature contributes to the β-adrenergic coronary vasodilation