S-nitrosoglutathione improves functional recovery in the isolated rat heart after cardioplegic ischemic arrest-evidence for a cardioprotective effect of nitric oxide.
The objective of this study was to assess the cardioprotective effect of the nitric oxide (.NO) donor, S-nitrosoglutathione (GSNO) and to investigate the mechanism of cardioprotection in a model of ischemia and reperfusion in isolated rat hearts. The role of .NO in myocardial protection was investigated by using nitronyl nitroxide as the .NO trap. Electron spin resonance spectroscopy was used to demonstrate that nitronyl nitroxide can trap .NO released from GSNO in a cardioplegic solution. .NO traps, oxyhemoglobin (4 mumol/l, n = 4) and nitronyl nitroxide (400 mumol/l, n = 5), inhibited the (2 mumol/l) GSNO-induced coronary vasodilation from the control value of 122% (n = 6) above base-line value to 73 and 60%, respectively. In the ischemia-reperfusion protocol, GSNO (20 mumol/l) was added to the cardioplegic solution during a 35-min ischemic arrest (n = 8). GSNO improved the functional recovery of ischemic hearts as compared to control (n = 6) as measured by the developed pressure (76 +/- 3 to 95 +/- 5% of base-line), rate pressure product (68 +/- 3 to 83 +/- 4% of base-line) and diastolic pressure (31 +/- 2 to 19 +/- 3 mm Hg). Reduction of coronary flow rate during reperfusion to control values in GSNO-treated hearts did not eliminate the improvement of functional recovery induced by GSNO. GSNO increased cyclic GMP production and slowed the accumulation of lactate (154 +/- 7 in control to 114 +/- 4 mumol/g dry wt.) and glucose-6-phosphate (3.66 +/- 0.19 in control to 2.18 +/- 0.10 mumol/g dry wt.) in myocardial tissue during ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Konorev
E A
EA
Biophysics Research Institute, Medical College of Wisconsin, Milwaukee, USA.
Tarpey
M M
MM
Joseph
J
J
Baker
J E
JE
Kalyanaraman
B
B
D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006019:Glycolysis; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006323:Heart Arrest / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D009603:Nitroso Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026422:S-Nitrosoglutathione; D013113:Spin Labels; D014665:Vasodilator Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
D009603:Nitroso Compounds; D013113:Spin Labels; D014665:Vasodilator Agents; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D005978:Glutathione; D006152:Cyclic GMP