Enhanced iNOS function in myocytes one day after brief ischemic episode.
There is increasing evidence that nitric oxide (NO) produced by inducible NO synthase (iNOS) plays a key role in cadioprotection during the "second window of protection" (SWOP). The goals of this study were to determine 1) whether a transient ischemic episode [10-min coronary artery occlusion (CAO), followed by full reperfusion] enhances NOS function in cardiac myocytes, 2) which specific NOS isoform is responsible for the enhanced NOS function in myocytes, and 3) to localize iNOS expression during SWOP. To address these questions, 10 dogs were instrumented to measure aortic and left ventricular pressures and wall thickness. At 1-2 wk after recovery, myocardial ischemia was induced regionally by a 10-min left circumflex CAO. After 24-h reperfusion, cardiac myocytes were isolated from the previously ischemic and nonischemic regions (n = 6). Myocyte contractile function was assessed using a video motion detector at 1 Hz (35 +/- 2 degrees C). At baseline, myocyte contractile function (% contraction) was similar in the two regions (ischemic 7.8 +/- 0.5% vs. nonischemic 7.8 +/- 0.2%). L-Arginine (1 mM) significantly reduced (P < 0.05) myocyte contraction in the ischemic (-34 +/- 3%, P < 0.05) but not (-7 +/- 4%) nonischemic regions; these responses were abolished by N(G)-nitro-L-arginine (1 mM), a nonspecific NOS inhibitor, as well as 2-amino-5,6-dihydro-6-methy-4H-1,3,thiazine (1 mM), a specific iNOS inhibitor. Immunohistochemistry also revealed enhanced iNOS expression in the myocardium and in particular the interstitial spaces in the ischemic zone. These results indicate that a brief ischemic episode upregulates iNOS function in myocytes as well as in the interstitial space between blood vessels and myocytes, strategically where it can regulate both vascular and myocyte function during the SWOP.
Kim
Song-Jung
SJ
Cardiovascular Research Institute and Department of Medicine, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark 07103, USA. kimso@umdnj.edu
Kim
Young-Kwon
YK
Takagi
Gen
G
Huang
Cheng-Hsiung
CH
Geng
Yong-Jian
YJ
Vatner
Stephen F
SF
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001794:Blood Pressure / Q000502:physiology; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000502:physiology; D007150:Immunohistochemistry; D019157:Ischemic Preconditioning, Myocardial; D007527:Isoenzymes / Q000032:analysis / Q000378:metabolism*; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000201:enzymology*; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D017202:Myocardial Ischemia / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D009599:Nitroprusside / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D017725:Ventricular Pressure / Q000502:physiology
D007527:Isoenzymes; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II