Nitric oxide production is maintained in exercising swine with chronic left ventricular dysfunction.
Left ventricular (LV) dysfunction caused by myocardial infarction (MI) is accompanied by endothelial dysfunction, most notably a loss of nitric oxide (NO) availability. We tested the hypothesis that endothelial dysfunction contributes to impaired tissue perfusion during increased metabolic demands as produced by exercise, and we determined the contribution of NO to regulation of regional systemic, pulmonary, and coronary vasomotor tone in exercising swine with LV dysfunction produced by a 2- to 3-wk-old MI. LV dysfunction resulted in blunted systemic and coronary vasodilator responses to ATP, whereas the responses to nitroprusside were maintained. Exercise resulted in blunted systemic and pulmonary vasodilator responses in MI that resembled the vasodilator responses in normal (N) swine following blockade of NO synthase with N(omega)-nitro-L-arginine (L-NNA, 20 mg/kg iv). However, L-NNA resulted in similar decreases in systemic (43 +/- 3% in N swine and 49 +/- 4% in MI swine), pulmonary (45 +/- 5% in N swine and 49 +/- 4% in MI swine), and coronary (28 +/- 4% in N and 35 +/- 3% in MI) vascular conductances in N and MI swine under resting conditions; similar effects were observed during treadmill exercise. Selective inhibition of inducible NO synthase with aminoguanidine (20 mg/kg iv) had no effect on vascular tone in MI. These findings indicate that while agonist-induced vasodilation is already blunted early after myocardial infarction, the contribution of endothelial NO synthase-derived NO to regulation of vascular tone under basal conditions and during exercise is maintained.
|Keywords||Adenosine Triphosphate/pharmacology, Animals, Coronary Circulation/drug effects, Coronary Vessels/drug effects, Endothelium, Vascular/physiopathology, Enzyme Inhibitors/pharmacology, Exertion/*physiology, Guanidines/pharmacology, Lung/blood supply, Myocardial Infarction/complications/physiopathology, Nitric Oxide Synthase Type II, Nitric Oxide Synthase/antagonists & inhibitors, Nitric Oxide/*biosynthesis/physiology, Nitroarginine/pharmacology, Nitroprusside/pharmacology, Reproducibility of Results, Research Support, Non-U.S. Gov't, Swine, Vasodilation/drug effects, Ventricular Dysfunction, Left/etiology/*physiopathology|
|Persistent URL||dx.doi.org/10.1152/ajpheart.00834.2001, hdl.handle.net/1765/13060|
Haitsma, D.B., Merkus, D., Vermeulen, J., Verdouw, P.D., & Duncker, D.J.G.M.. (2002). Nitric oxide production is maintained in exercising swine with chronic left ventricular dysfunction.. American Journal of Physiology - Heart and Circulatory Physiology, 2198–2209. doi:10.1152/ajpheart.00834.2001