L-arginine, a nitric oxide precursor, attenuates ischemia-reperfusion injury by inhibiting inositol-1,4,5-triphosphate.
OBJECTIVE
We evaluated the effect of pretreatment with nitric oxide precursor before ischemia on recovery with reperfusion in rat hearts.


METHODS
Isolated rat hearts were perfused with Krebs-Henseleit buffer without (C group) or with 3 mmol/L L-arginine (A group) before 30 minutes of ischemia. The left ventricular function, including heart rate, developed pressure, maximal dp/dt, and coronary flow, were measured before pretreatment and after 10 and 30 minutes of reperfusion. Cyclic guanosine monophosphate (by radioimmunoassay), calcium (by absorption spectrophotometry), and inositol 1,4,5-triphosphate synthesized from tritiated myo-inositol (by ion-exchange chromatography preceding counting) were measured at the same times and immediately after ischemia.


RESULTS
Recovery of ventricular function was significantly greater in the A group than in the C group. Pretreatment increased postischemic cyclic guanosine monophosphate content compared with the preischemic level (from 1.06 +/- 0.12 to 1.94 +/- 0.09 pmol/mg protein, p < 0.05). No change in cyclic guanosine monophosphate was evident in the C group. In the C group, inositol triphosphate content increased after 10 minutes of reperfusion beyond the preischemic level (from 0.53 +/- 0.023 to 1.15 +/- 0.045 cpm x 10(-3)/gm, p < 0.05) as did calcium at 30 minutes (from 4.12 +/- 0.164 to 6.86 +/- 0.544 mmol/gm dry weight). In the A group, both of these increases were significantly attenuated.


CONCLUSIONS
These data suggest that L-arginine pretreatment may reduce calcium overload by increasing cyclic guanosine monophosphate production, which in turn downregulates inositol triphosphate synthesis during reperfusion.
Mizuno
T
T
Department of Thoracic and Cardiovascular Surgery, School of Medicine, Tokyo Medical and Dental University, Japan.
Watanabe
M
M
Sakamoto
T
T
Sunamori
M
M
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D015536:Down-Regulation; D015544:Inositol 1,4,5-Trisphosphate / Q000037:antagonists & inhibitors*; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D010477:Perfusion; D011292:Premedication; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
D009569:Nitric Oxide; D015544:Inositol 1,4,5-Trisphosphate; D001120:Arginine; D006152:Cyclic GMP; D002118:Calcium