COX-2 and iNOS in opioid-induced delayed cardioprotection in the intact rat. Life Sci 2004 May 28;75(2):129-40
Date
05/04/2004Pubmed ID
15120566DOI
10.1016/j.lfs.2003.10.036Scopus ID
2-s2.0-2142828491 (requires institutional sign-in at Scopus site) 46 CitationsAbstract
Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) have been previously implicated in the late phase of cardioprotection associated with opioid-induced and ischemic preconditioning (IPC) in conscious rabbits and COX-2 in isolated rat hearts pretreated with an exogenous delta opioid agonist. However, it is not know if both iNOS and COX-2 mediate the late phase of cardioprotection induced by opioids in the intact blood-perfused rat. Therefore, we investigated the role of COX-2 and iNOS in the delayed phase of protection mediated by delta opioid receptor activation. Rats were pretreated 24 hours prior to an occlusion/reperfusion protocol with the selective non-peptide delta opioid agonists, BW373U86 (BW) and SNC-121 (SNC). NS-398, a selective COX-2 inhibitor was administered after the 24-hour recovery period just prior to index ischemia. The selective iNOS inhibitors, S-methylthiourea (SMT) and aminoguanidine (AG), were administered in conjunction with opioid pretreatment or were also given 24 hours after opioid administration just prior to index ischemia. COX-2 inhibition by NS-398 given 24 hours after opioid administration attenuated the protective effects of both BW and SNC (46 +/- 6 vs. 13 +/- 3 and 51 +/- 5 vs. 29 +/- 2, p < 0.001, respectively). Similarly, inhibition of iNOS following 24 hours of treatment with opioids also attenuated the protective effects of BW and SNC. However, the delayed protective effects of the opioids were not attenuated by pretreatment with the iNOS inhibitors 24 hours prior to the infarct protocol. These results suggest that both COX-2 and iNOS are mediators of delayed protection induced by non-peptide delta opioid agonists. It appears that the trigger effect is not dependent on the activity of iNOS or COX-2 but the late phase of cardioprotection is dependent on the upregulation of these enzymes.
Author List
Patel HH, Hsu AK, Gross GJMESH terms used to index this publication - Major topics in bold
Analysis of VarianceAnimals
Benzamides
Blood Pressure
Cardiotonic Agents
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Dose-Response Relationship, Drug
Guanidines
Heart Rate
Ischemic Preconditioning, Myocardial
Isoenzymes
Isothiuronium
Male
Myocardial Reperfusion Injury
Myocardium
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Nitrobenzenes
Piperazines
Prostaglandin-Endoperoxide Synthases
Rats
Rats, Sprague-Dawley
Receptors, Opioid, delta
Sulfonamides
