Cardioprotection and attenuation of endothelial dysfunction by organic nitric oxide donors in myocardial ischemia-reperfusion.

Abstract

The effects of two nitric oxide (NO) donors were evaluated in a 6-h model of feline myocardial ischemia-reperfusion. After 80 min of a 90-min ischemic period, SIN-1 or C87-3754 or their respective controls (i.e., 0.9% NaCl or C88-3934, a control compound which does not release NO) were given i.v. as a bolus (0.1 mg/kg) and infused at 1 mg/kg/h for the entire 4.5-h reperfusion period. Administration of the active NO donors significantly decreased the necrotic area/area-at-risk ratio from 29 +/- 3% in the vehicle group to 9 +/- 2 and 11 +/- 5% in the SIN-1 and C87-3754 groups, respectively (P less than .001). The inactive NO donor C88-3934 failed to reduce infarct size (31 +/- 3%). Neither NO donor reduced the accumulation of neutrophils in the necrotic area when compared to their respective control groups, but both agents significantly attenuated coronary endothelial dysfunction as shown by a vasorelaxation to acetylcholine of 62 +/- 2 and 64 +/- 3% in the SIN-1- and C87-3754-treated arteries, as compared to only a 27 +/- 3 and 34 +/- 4% vasorelaxation in the vehicle and inactive NO donor groups, respectively (P less than .001). Our studies show that SIN-1 and C87-3754 exert beneficial effects in a 6-h model of myocardial ischemia-reperfusion. Both NO donors decreased myocardial necrosis and decreased the reperfusion-induced endothelial dysfunction without significantly altering the pressure-rate index (i.e., an index of myocardial oxygen demand).

• Authors: M R Siegfried, J Erhardt, T Rider, X L Ma, A M Lefer
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 260 Issue 2 Pg. 668-75 (Feb 1992) ISSN: 0022-3565 [Print] United States
• PMID: 1738117 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Prostaglandin Endoperoxides, Synthetic
• Sydnones
• Vasodilator Agents
• 3-(cis-2,6-dimethylpiperidino)sydnonimine
• Nitric Oxide
• Calcimycin
• linsidomine
• 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
• Molsidomine
• Acetylcholine

Topics

• 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
• Acetylcholine (pharmacology)
• Animals
• Calcimycin (pharmacology)
• Cats
• Endothelium, Vascular (drug effects, physiopathology)
• Hemodynamics (drug effects)
• Hydrogen-Ion Concentration
• In Vitro Techniques
• Male
• Molsidomine (analogs & derivatives, pharmacology, therapeutic use)
• Muscle Relaxation (drug effects)
• Muscle, Smooth, Vascular (drug effects, physiology)
• Myocardial Reperfusion Injury (prevention & control)
• Nitric Oxide (pharmacology)
• Prostaglandin Endoperoxides, Synthetic (pharmacology)
• Sydnones (pharmacology, therapeutic use)
• Vasodilator Agents (pharmacology)