Nitric oxide: a trigger for classic preconditioning?

Am J Physiol Heart Circ Physiol. 2000 Dec;279(6):H2752-65. doi: 10.1152/ajpheart.2000.279.6.H2752.

Abstract

To determine whether nitric oxide (NO) is involved in classic preconditioning (PC), the effect of NO donors as well as inhibition of the L-arginine-NO-cGMP pathway were evaluated on 1) the functional recovery during reperfusion of ischemic rat hearts and 2) cyclic nucleotides during both the PC protocol and sustained ischemia. Tissue cyclic nucleotides were manipulated with NO donors [S-nitroso-N-penicillamine (SNAP), sodium nitroprusside (SNP), or L-arginine] and inhibitors of nitric oxide synthase (N(omega)-nitro-L-arginine methyl ester or N-nitro-L-arginine) or guanylyl cyclase (1H-[1,2,4]oxadiazolol-[4,3-a]quinoxaline-1-one). Pharmacological elevation in tissue cGMP levels by SNAP or SNP before sustained ischemia elicited functional improvement during reperfusion comparable to that by PC. Administration of inhibitors before and during the PC protocol partially attenuated functional recovery, whereas they had no effect when given after the ischemic PC protocol and before sustained ischemia only, indicating a role for NO as a trigger but not as a mediator. Ischemic PC, SNAP, or SNP caused a significant increase in cGMP and a reduction in cAMP levels after 25 min of sustained ischemia that may contribute to the protection obtained. The results obtained suggest a role for NO (and cGMP) as a trigger in classic PC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Monophosphate / metabolism
  • Animals
  • Cyclic GMP / metabolism
  • Enzyme Inhibitors / pharmacology
  • Epinephrine / pharmacology
  • Guanylate Cyclase / antagonists & inhibitors
  • Guanylate Cyclase / metabolism
  • In Vitro Techniques
  • Ischemic Preconditioning, Myocardial*
  • Male
  • Myocardial Contraction / drug effects
  • Myocardial Contraction / physiology
  • Myocardial Ischemia / drug therapy
  • Myocardial Ischemia / metabolism*
  • Myocardium / enzymology
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / metabolism*
  • Nitric Oxide Donors / pharmacology
  • Nitric Oxide Synthase / metabolism
  • Nitroarginine / pharmacology
  • Nitroprusside / pharmacology
  • Oxadiazoles / pharmacology
  • Penicillamine / analogs & derivatives*
  • Penicillamine / pharmacology
  • Quinoxalines / pharmacology
  • Rats
  • Rats, Wistar
  • S-Nitroso-N-Acetylpenicillamine
  • Sympathomimetics / pharmacology
  • Vasodilator Agents / pharmacology

Substances

  • 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one
  • Enzyme Inhibitors
  • Nitric Oxide Donors
  • Oxadiazoles
  • Quinoxalines
  • Sympathomimetics
  • Vasodilator Agents
  • Nitroprusside
  • Nitroarginine
  • Nitric Oxide
  • Adenosine Monophosphate
  • S-Nitroso-N-Acetylpenicillamine
  • Nitric Oxide Synthase
  • Guanylate Cyclase
  • Penicillamine
  • Cyclic GMP
  • NG-Nitroarginine Methyl Ester
  • Epinephrine