nitroarginine and pirsidomine

The aim of this study was to determine whether the acute inhibition of nitric oxide (NO) synthase causes changes in cardiac substrate utilization which can be reversed by a NO donor.. NO synthase was blocked by giving 30 mg/kg of nitro-L-arginine (NLA) i.v. to 15 chronically instrumented dogs. Hemodynamics and blood samples from aorta and coronary sinus were taken at control and at 1 and 2 h after NLA. In five dogs, 0.4 mg/kg of the NO donor 3754 was given i.v. 1 h after NLA. In six dogs, angiotensin II was infused over 2 h (20-40 ng/kg/min) to mimic the hemodynamic effects of NLA.. Two h after NLA: mean arterial pressure was 153 +/- 4 mmHg; MVO2 increased by 38%; cardiac uptake of lactate and glucose increased, respectively, from 20.0 +/- 5.0 to 41.0 +/- 9.3 mumol/min and from 1.1 +/- 0.7 to 6.8 +/- 1.5 mg/min (all P < 0.05 vs. control). Cardiac uptake of free fatty acids decreased by 43% after 1 h (P < 0.05) and returned to control values at 2 h. Cardiac respiratory quotient increased from 0.76 +/- 0.03 to 1.05 +/- 0.07, indicating a shift to carbohydrate oxidation. All these changes were reversed by the NO donor. In the dogs receiving angiotensin II infusion, MVO2 increased by 28% and lactate uptake doubled (both P < 0.05), but no other metabolic changes where observed.. The acute inhibition of NO synthase by NLA causes a switch from fatty acids to lactate and glucose utilization by the heart which can be reversed by a NO donor, suggesting an important regulatory action of NO on cardiac metabolism.

Topics: Analysis of Variance; Angiotensin II; Animals; Blood Pressure; Coronary Circulation; Dogs; Fatty Acids, Nonesterified; Glucose; Insulin; Lactic Acid; Male; Myocardium; Nitric Oxide; Nitric Oxide Donors; Nitric Oxide Synthase; Nitroarginine; Oxygen Consumption; Sydnones; Time Factors