Initiation of microvascular protection by nitric oxide in late preconditioning

The authors hypothesized that nitric oxide is induced by a brief period of ischemia/reperfusion (ischemic preconditioning, IPC) on postoperative day ( POD) 1, and that this released nitric oxide is responsible for initiating a delayed microvascular protection against a prolonged period of ischemia in skeletal muscle on POD day 2. The cremaster muscle of male Sprague-Dawley rats underwent 4 hr of ischemia, and then 60 min of reperfusion. IPC consis ted of 45 min of ischemia but was done 24 hr before the prolonged ischemia. Local intraarterial infusion of sodium nitroprusside (SNP, a donor of nitr ic oxide) or N-w-nitro-(L)-arginine (L-NA, a nonselective nitric oxide synt hase antagonist) were also given 24 hr before prolonged ischemia. Arteriole diameters and capillary perfusion were measured using intravital microscop y. Four groups were compared: 1) control; 2) IPC: 3) SNP + sham IPC; and 4) L-NA + IPC. Four hours of ischemia followed by reperfusion created a signi ficant vasoconstriction and capillary no-reflow in the microcirculation of cremaster muscles. These alterations were largely prevented by IPC. Local i ntraarterial infusion of SNP without IPC created a similar microvascular pr otection to that induced by IPC alone. In contrast, intraarterial infusion of L-NA prior to IPC eliminated the IPC-induced microvascular protection. I n conclusion, in late preconditioning, nitric oxide contributes to the init iation of a delayed microvascular protection against prolonged ischemia in skeletal muscle.