INCREASED AORTIC BLOOD-PRESSURE CONTRIBUTES TO POTENTIATED DOBUTAMINEINOTROPIC RESPONSES AFTER SYSTEMIC NO SYNTHASE INHIBITION IN SHEEP

Objective: To determine whether inotropic responses to the beta-adrene rgic agonist dobutamine are potentiated by systemic inhibition of nitr ic oxide synthase (NOS) with the L-arginine analogue N-omega-nitro-L-a rginine (L-NNA), and to establish to what extent any observed response s are related to the increase in aortic blood pressure accompanying sy stemic NOS inhibition. Methods: Dobutamine was infused incrementally a t rates of 1, 2.5, 5 and 10 mu g/kg/min in 15 open-chest, anaesthetise d ewes before and after inhibition of NO synthesis with i.v. L-NNA (n = 8), or elevation of mean aortic blood pressure to the same extent as attained with NOS inhibition using proximal arterial occlusion (n = 7 ). Results: By the peak infusion rate, dobutamine increased the maxima l rate of rise of left ventricular pressure (LV dP/dt(MAX)) by 100% (p <0.001) and reduced LV stroke work by 18% (p <0.01). L-NNA and arteria l occlusion increased resting mean aortic blood pressure by 55+/-4 and 51+/-3 mmHg respectively. Compared to dobutamine alone, subsequent pe ak dobutamine-related increases in LV dP/dt(MAX) were augmented by 76% after L-NNA and by 88% after arterial occlusion (both p<0.001). Moreo ver, dobutamine increased LV stroke work, by 23% at infusion rates of 1-5 mu g/kg/min (p<0.001) after L-NNA, and by 17% at an infusion rate of 1 mu g/kg/min (p<0.01) after arterial occlusion. Conclusions: Syste mic NOS inhibition potentiates the effects of dobutamine on LV isovolu mic and pumping performance in the intact circulation, but this potent iation is in large part related to the increase in arterial blood pres sure accompanying NOS inhibition. (C) 1998 Elsevier Science B.V. All r ights reserved.