© 1995 by European Society of Cardiology
Copyright © 1995, European Society of Cardiology
Endogenous nitric oxide (NO) protects against ischaemia-reperfusion injury in the rabbit
aDepartment of Cardiothoracic Surgery, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27157-1096, USA
bDepartment of Physiology/Pharmacology, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27157-1096, USA
c4201 St. Antoine, Detroit, MI 48201, USA
* Corresponding author. Tel. (4-1-910) 716-3084; (+1-910) 716-3348.
Objectives: Recent studies suggest that nitric oxide (NO) is deleterious in models of shock and hypoxia-reoxygenation However, the role of endogenous NO in ischaemia-reperfusion injury in vivo remains controversial. We tested the hypothesis that blockade of endogenous NO produced during myocardial ischaemia-reperfusion or during reperfusion alone in vivo increases infarct size after coronary occlusion in the rabbit, and conversely, supplementation with L-arginine would reduce infarct size. Methods: Ketamine-xylazine anaesthetised New Zealand white rabbits were subjected to left coronary artery occlusion for 30 min and reperfusion for 120 min. The rabbits were divided into five groups: (1) saline (VEH); (2) L-nitro arginine (L-NA), a NO-synthase inhibitor, was infused intravenously (15 mg/kg bolus followed by 7.5 mg/kg h–1) before coronary occlusion to block NO synthase activity during ischaemia and reperfusion (IR); (3) L-NA was administered during reperfusion only (R) at the same dose as in the IR group; (4) D-arginine (D-ARG) (25 mg/kg bolus followed by 4 mg/kg min–1), the non-metabolised enantiomer of L-arginine was infused intravenously during reperfusion only; (5) L-arginine (L-ARG) (25 mg/kg bolus followed by 4 mg/kg min–1), the physiological precursor of NO, was infused intravenously during reperfusion only. Results: L-NA infusion in the IR and R groups caused an increase in mean arterial pressure and a decrease in heart rate; however, no significant change in pressure rate product (PRP) occurred immediately after drug infusion. PRP did not change significantly during the experiment across groups except at the end of reperfusion. The area at risk was comparable in all groups, averaging 29(1)%. The infarct size (triphenyltetrazolium chloride) expressed as a percent of area at risk was 27(2)% for the untreated vehicle group. In contrast, L-NA significantly (P < 0.05) increased infarct size in the IR group, 51(2)%; this augmented infarct size persisted when NO synthase activity was blocked during reperfusion only in the R group, 50(2)%. There was no significant (P < 0.05) difference in infarct size between the IR and the R groups. D-ARG-treated group showed a comparable increase in infarct size 48(2)% versus the IR and R groups. However, supplementation of NO with L-arginine (L-ARG) showed no reduction in infarct size, 24(3)%, over vehicle group (VEH). Conclusions: We conclude that (1) blockade of NO synthase activity with L-NA increases infarct size, (2) this effect was expressed primarily during reperfusion, (3) D-arginine mimicked the infarct augmentation of L-NA, while (4) L-arginine supplementation did not reduce infarct size. These data imply that endogenous NO production exerts a tonic cardioprotective effect on myocardial infarct following coronary reperfusion.
KEYWORDS NO-synthase antagonists; L-Nitro-arginine; D-Arginine; L-Arginine; Myocardial infarct size; Triphenyltetrazolium chloride; Rabbit heart; Reperfusion
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  G. Ambrosio, M. Del Pinto, I. Tritto, G. Agnelli, M. Bentivoglio, C. Zuchi, F. A. Anderson, J. M. Gore, J. Lopez-Sendon, A. Wyman, et al. Chronic nitrate therapy is associated with different presentation and evolution of acute coronary syndromes: insights from 52 693 patients in the Global Registry of Acute Coronary Events Eur. Heart J., November 10, 2009; (2009) ehp457v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Schulz, M. Kelm, and G. Heusch Nitric oxide in myocardial ischemia/reperfusion injury Cardiovasc Res, February 15, 2004; 61(3): 402 - 413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-P. Wang, C. Sato, K. Mizoguchi, Y. Yamashita, M. Oe, and H. Maeta Lipopolysaccharide triggers late preconditioning against myocardial infarction via inducible nitric oxide synthase Cardiovasc Res, October 1, 2002; 56(1): 33 - 42. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Mori, N. Haramaki, H. Ikeda, and T. Imaizumi Intra-coronary administration of L-arginine aggravates myocardial stunning through production of peroxynitrite in dogs Cardiovasc Res, October 1, 1998; 40(1): 113 - 113. [Abstract] [Full Text] [PDF]
|
|