ADAPTATION OF MYOCARDIAL BLOOD-FLOW TO INCREASED METABOLIC DEMAND IS NOT DEPENDENT ON ENDOTHELIAL VASODILATORS IN THE RAT-HEART

Objective-To investigate the role of endothelial vasodilating factors in adaptation of myocardial blood flow to increased metabolic demands. Design-Alterations in the effects of endothelium dependent (acetylcho line) and independent (sodium nitroprusside) vasodilators and the beta (1) receptor agonist dobutamine were studied after inhibition of endot helium derived relaxing factor (EDRF) with L-N-G-nitro-arginine methyl ester (L-NAME), prostanoid synthesis with indomethacin, and ATP sensi tive potassium channels with glibenclamide. Experimental animals-Femal e Wistar rats, in situ perfused heart. Main outcome measures-Myocardia l blood flow (H-2 clearance); systolic fractional thickening (pulsed D oppler); mean arterial blood pressure. Results-L-NAME reduced myocardi al blood flow by 58 (12)% (mean (SD), P < 0 . 001) and systolic thicke ning fraction (FT) by 36 (9)% (P < 0 . 05). These effects were signifi cantly reversed by administration of L-arginine but not D-arginine. Pr etreatment with L-NAME inhibited the increase in myocardial blood flow caused by acetylcholine (control: +42 (9)%; L-NAME: -29 (7)%, P < 0 . 001) but did not affect the increase in myocardial blood flow caused by sodium nitroprusside (control: +44 (5)%; L-NAME: +34 (10)%, NS). Pr etreatment with L-NAME did not change the effect of dobutamine on myoc ardial blood flow (+61 (3)%) and FT (+32 (8)%) compared with baseline values (P < 0 . 001). Neither pretreatment with indomethacin nor with glibenclamide reduced the dobutamine induced increase in myocardial bl ood flow. Conclusions-Inhibition of EDRF, prostanoid synthesis, and AT P sensitive potassium channels did not reduce the vasodilator reserve during increased metabolic demands induced by beta(1) adrenergic stimu lation. Therefore, adaptation of myocardial blood flow to increased me tabolic demands is independent of endothelial relaxing factors in the rat heart.