Stimulation of endogenous nitric oxide pathway by L-arginine reduces declamp mortality and attenuates hypertension associated with aortic cross-clamp-induced hindlimb ischemia in rats.
We tested the hypotheses that maintaining the activity of nitric oxide by L-arginine infusion would counteract the release of an endogenous nitric oxide synthase inhibitor, improve survival, and decrease intraoperative hypertension after infrarenal aortic cross-clamp surgery. Hindlimb ischemia was generated by infrarenal aortic cross-clamping and tying of the left femoral artery for 5 hours in rats with bilateral femoral and sciatic nerves cut. Mean blood pressure significantly increased during the 5-hour ischemic period in ischemic rats (no drug treatment). Baroreceptor function was inhibited in ischemic rats assessed by intravenous dose response to phenylephrine and nitroprusside after 5 hours of ischemia, suggesting baroreceptor resetting. In ischemic rats infused with L-arginine the intraoperative hypertension was prevented during the 5-hour period, suggesting that this hypertension may be mediated by nitric oxide inhibition. The rates of survival and arrhythmias 2 hours after declamping were 50% in ischemic rats and 100% in ischemic rats treated with N omega-nitro-L-arginine (a nitric oxide synthase inhibitor) 10 minutes before declamping. In ischemic rats infused with L-arginine the survival rate was significantly increased to 100% and the arrhythmic rate was inhibited. We conclude that L-arginine prevents hypertension during cross-clamping and decreases the mortality rate and arrhythmias after declamping by maintaining nitric oxide synthesis. These results suggest that humoral factors released from the ischemic hindlimb may inhibit endogenous nitric oxide production, thus contributing to intraoperative hypertension, arrhythmias, and high mortality rate after aortic cross-clamp surgery.
Jin
J S
JS
Department of Physiology, University of Michigan Medical School, Ann Arbor, 48109-0622, USA.
D'Alecy
L G
LG
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology*; D006614:Hindlimb / Q000098:blood supply; D006973:Hypertension / Q000517:prevention & control*; D007511:Ischemia / Q000150:complications*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine; D011311:Pressoreceptors / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine