Cardioprotective effects of nitric oxide-aspirin in myocardial ischemia-reperfused rats.

Abstract

In this study, the cardioprotective effects of nitric oxide (NO)-aspirin, the nitroderivative of aspirin, were compared with those of aspirin in an anesthetized rat model of myocardial ischemia-reperfusion. Rats were given aspirin or NO-aspirin orally for 7 consecutive days preceding 25 min of myocardial ischemia followed by 48 h of reperfusion (MI/R). Treatment groups included vehicle (Tween 80), aspirin (30 mg.kg(-1).day(-1)), and NO-aspirin (56 mg.kg(-1).day(-1)). NO-aspirin, compared with aspirin, displayed remarkable cardioprotection in rats subjected to MI/R as determined by the mortality rate and infarct size. Mortality rates for vehicle (n = 23), aspirin (n = 22), and NO-aspirin groups (n = 22) were 34.8, 27.3, and 18.2%, respectively. Infarct size of the vehicle group was 44.5 +/- 2.7% of the left ventricle (LV). In contrast, infarct size of the LV decreased in the aspirin- and NO-aspirin-pretreated groups, 36.7 +/- 1.8 and 22.9 +/- 4.3%, respectively (both P < 0.05 compared with vehicle group; P < 0.05, NO-aspirin vs. aspirin ). Moreover, NO-aspirin also improved ischemia-reperfusion-induced myocardial contractile dysfunction on postischemic LV developed pressure. In addition, NO-aspirin downregulated inducible NO synthase (iNOS; 0.37-fold, P < 0.01) and cyclooxygenase-2 (COX-2; 0.61-fold, P < 0.05) gene expression compared with the vehicle group after 48 h of reperfusion. Treatment with N(G)-nitro-L-arginine methyl ester (L-NAME; 20 mg/kg), a nonselective NOS inhibitor, aggravated myocardial damage in terms of mortality and infarct size but attenuated effects when coadministered with NO-aspirin. L-NAME administration did not alter the increase in iNOS and COX-2 expression but did reverse the NO-aspirin-induced inhibition of expression of the two genes. The beneficial effects of NO-aspirin appeared to be derived largely from the NO moiety, which attenuated myocardial injury to limit infarct size and better recovery of LV function following ischemia and reperfusion.

• Authors: Yilong Fu, Zhongjing Wang, Woei Lee Chen, Philip K Moore, Yi Zhun Zhu
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 293 Issue 3 Pg. H1545-52 (Sep 2007) ISSN: 0363-6135 [Print] United States
• PMID: 17526656 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Enzyme Inhibitors
• RNA, Messenger
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type II
• Cyclooxygenase 1
• Cyclooxygenase 2
• nitroaspirin
• Aspirin
• NG-Nitroarginine Methyl Ester

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology, therapeutic use)
• Aspirin (analogs & derivatives, pharmacology, therapeutic use)
• Blood Pressure (drug effects, physiology)
• Cyclooxygenase 1 (genetics, metabolism)
• Cyclooxygenase 2 (genetics, metabolism)
• Enzyme Inhibitors (pharmacology)
• Heart Rate (drug effects, physiology)
• Male
• Myocardial Infarction (pathology)
• Myocardial Reperfusion Injury (metabolism, physiopathology, prevention & control)
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitric Oxide Synthase (antagonists & inhibitors, genetics, metabolism)
• Nitric Oxide Synthase Type II (genetics, metabolism)
• RNA, Messenger (genetics, metabolism)
• Random Allocation
• Rats
• Rats, Wistar
• Ventricular Dysfunction, Left (metabolism, physiopathology, prevention & control)
• Ventricular Function, Left (drug effects, physiology)