title: Nitric oxide controls cardiac substrate utilization in the conscious dog.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Physiology, New York Medical College, Valhalla 10595, USA.
authors.forename: F A
authors.initials: FA
authors.lastname: Recchia
authors.forename: P I
authors.initials: PI
authors.lastname: McConnell
authors.forename: K E
authors.initials: KE
authors.lastname: Loke
authors.forename: X
authors.initials: X
authors.lastname: Xu
authors.forename: M
authors.initials: M
authors.lastname: Ochoa
authors.forename: T H
authors.initials: TH
authors.lastname: Hintze
mesh_terms: D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000097:blood; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D013558:Sydnones / Q000494:pharmacology; D013997:Time Factors
chemical_list: D005230:Fatty Acids, Nonesterified; D007328:Insulin; D020030:Nitric Oxide Donors; D013558:Sydnones; D000804:Angiotensin II; D019335:Nitroarginine; D009569:Nitric Oxide; D019344:Lactic Acid; C073303:pirsidomine; D019001:Nitric Oxide Synthase; D005947:Glucose