Increased aortic blood pressure contributes to potentiated dobutamine inotropic responses after systemic NO synthase inhibition in sheep.
OBJECTIVE
To determine whether inotropic responses to the beta-adrenergic agonist dobutamine are potentiated by systemic inhibition of nitric oxide synthase (NOS) with the L-arginine analogue N omega-nitro-L-arginine (L-NNA), and to establish to what extent any observed responses are related to the increase in aortic blood pressure accompanying systemic NOS inhibition.


METHODS
Dobutamine was infused incrementally at rates of 1, 2.5, 5 and 10 micrograms/kg/min in 15 open-chest, anaesthetised 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 maximal rate of rise of left ventricular pressure (LV dP/dtMAX) by 100% (p < 0.001) and reduced LV stroke work by 18% (p < 0.01). L-NNA and arterial occlusion increased resting mean aortic blood pressure by 55 +/- 4 and 51 +/- 3 mmHg respectively. Compared to dobutamine alone, subsequent peak dobutamine-related increases in LV dP/dtMAX were augmented by 76% after L-NNA and by 88% after arterial occlusion (both p < 0.001). Moreover, dobutamine increased LV stroke work by 23% at infusion rates of 1-5 micrograms/kg/min (p < 0.001) after L-NNA, and by 17% at an infusion rate of 1 microgram/kg/min (p < 0.01) after arterial occlusion.


CONCLUSIONS
Systemic NOS inhibition potentiates the effects of dobutamine on LV isovolumic and pumping performance in the intact circulation, but this potentiation is in large part related to the increase in arterial blood pressure accompanying NOS inhibition.
Penny
D J
DJ
Institute of Reproduction and Development, Monash University, Clayton, Victoria, Australia.
Chen
H
H
Smolich
J J
JJ
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001011:Aorta / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D004280:Dobutamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008026:Ligation; D009200:Myocardial Contraction / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology; D012756:Sheep; D013268:Stimulation, Chemical; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D019335:Nitroarginine; D004280:Dobutamine; D019001:Nitric Oxide Synthase