title: Divergent effects of NO synthase inhibition on systemic and myocardial O2 delivery and consumption during dobutamine infusion in sheep.
abstract: It is unknown if nitric oxide (NO) modulates the balance between systemic or myocardial O2 delivery ( DO2) and consumption VO2 during inotropic stimulation with the beta-adrenergic agonist dobutamine. Accordingly, we measured systemic and left ventricular (LV) DO2 and during dobutamine infusion to a peak of 10 microg .kg-1 .min-1, before and after inhibition of NO synthesis with i.v. N(omega)-nitro- L-arginine ( L-NNA, 25 mg.kg-1) in 11 anesthetized ewes instrumented with aortic, pulmonary arterial and coronary sinus catheters, an ultrasonic coronary artery flow probe and a pulmonary arterial thermistor to measure cardiac output. L-NNA reduced systemic DO2 by 19% (2.1+/-0.5 ml.min-1.kg-1, P<0.005) but increased systemic by 13% (0.4+/-0.1 ml.in-1.g-1, P<0.05), whereas LV DO2 and rose by 44% (4.3+/-1.3 ml.min-1).100 g-1, P<0.005) and 47% (3.1+/-0.9.min-1.100 g-1, P<0.025) respectively. Dobutamine increased systemic DO2 by 61% (5.3+/-0.9 ml.min-1.kg-1, P<0.001) and systemic by 10% (0.32+/-0.12 ml.min-1.kg-1, P<0.01), with no effect of L-NNA on either response ( P>0.9). As a result, while was 0.5 ml.min(-1).kg-1 higher at any given level of DO2 ( P<0.001), the slope of the systemic DO2- relation was unchanged after L-NNA. By contrast, LV DO2 increased by 152% (15.6+/-2.2 ml.min-1.100 g-1, P<0.001) and by 184% (12.7+/-1.9 ml.min-1.100 g-1, P<0.001), but because the slope of both dose-response curves was reduced by 48% after L-NNA ( P<0.001), the LV DO2- relationship was unaffected by inhibition of NO synthesis. These results suggest that NO modulated the baseline balance between systemic, but not myocardial, DO2 and. However, NO did not additionally alter dobutamine-related changes in either systemic or myocardial DO2 and balance.
authors.affiliation: Department of Cardiology, Royal Children's Hospital, Parkville, 3052, Victoria, Australia.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Penny
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Smolich
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D004280:Dobutamine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects* / Q000502:physiology; D012756:Sheep
chemical_list: D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D019335:Nitroarginine; D004280:Dobutamine; D019001:Nitric Oxide Synthase; D010100:Oxygen