The opposing effects of an inhibitor of nitric oxide synthesis and of a donor of nitric oxide in rabbits undergoing myocardial ischemia reperfusion.
We observed that N-nitro-L-arginine (NOLA), a nitric oxide biosynthesis inhibitor, exacerbated necrosis in the rabbit heart during ischemia-reperfusion while 3-morpholino-sydnonimine-hydrochloride (SIN-1) (a nitric oxide donor) reduced myocardial damage in the same model. In rabbits undergoing 1-h ligation of the anterior ventricular coronary artery, a single bolus injection of NOLA (30 mg/kg) or continuous infusion of SIN-1 (3 mg/kg) were introduced into the post-ischemic heart immediately before 4-h reperfusion. Against negligible necrosis in 6 sham-operated control animals, and 33.8 (SD 13.5)% necrosis in the area at risk for the saline control group (n = 8), the NOLA-treated group (n = 8) had a necrosis of 44.3 (SD 8.6)% whereas the SIN-1-treated group (n = 10) showed a necrosis of 16.8 (SD 4.9)% (both with p < 0.05 vs saline control group). The pressure-rate index increased in the NOLA-treated group but decreased in the SIN-1-treated group. These data support the contention that a nitric oxide donor is an effective cardioprotector during ischemia-reperfusion in vivo.
Fung
K P
KP
Department of Clinical Biochemistry, University of Toronto, Canada.
Wu
T W
TW
Zeng
L H
LH
Wu
J
J
D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000633:toxicity; D001794:Blood Pressure / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000473:pathology*; D009336:Necrosis; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000494:pharmacology*; D019335:Nitroarginine; D011817:Rabbits; D012016:Reference Values; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D019335:Nitroarginine; D009569:Nitric Oxide; C002385:linsidomine; D001120:Arginine; D008981:Molsidomine