Effects of L-NAME and L-arginine on ischemia-reperfusion injury in rat skeletal muscle

The involvement of nitric oxide in ischemia-reperfusion injury remains cont roversial and has been reported to be both beneficial and deleterious, depe nding on the tissue and model used. This study evaluated the effects of the nitric oxide synthase inhibitor-N-G-nitro-L-arginine-methyl ester (L-NAME) and the substrate for nitric oxide synthase, L-arginine on skeletal muscle ne crosis in a rat model of ischemia-reperfusion injury. The rectus femori s muscle in male Wistar rats (250 to 500 g) was isolated on its vascular pe dicle and subjected to 4 hours of complete arteriovenous occlusion. The ani mals were divided into five groups: (1) sham-raised control, no ischemia, n o treatment (n = 6); (2) 4 hours of ischemia (n = 6); (3) vehicle control, 4 hours of ischemia + saline (n = 6); (4) 4 hours of ischemia + L-arginine infusion (n = 6); and (5) 4 hours of ischemia + L-NAME infusion (n = 6). Th e infusions (10 mg/kg) were administered into the contralateral femoral vei n beginning 5 minutes before reperfusion and during the following 30 to 45 minutes, Upon reperfusion, the muscle was sutured in its anatomic position and all wounds were closed. The percentage of muscle necrosis was assessed after 24 hours of reperfusion by serial transections, nitroblue tetrazolium staining, digital photography, and computerized planimetry. Sham (group 1) animals sustained baseline necrosis of 11.9 +/- 3.0 (percentage necrosis /- SEM). Four hours of ischemia (group 2) significantly increased necrosis to 79.2 +/- 1.4 (P < 0.01). Vehicle control (group 3) had no significant di fference in necrosis (81.17 +/- 5.0) versus untreated animals subjected to 4 hours of ischemia (group 2). Animals treated with L-arginine (group 4) ha d significantly reduced necrosis to 34.6 +/- 7.5 versus untreated (group 2) animals (p < 0.01). Animals infused with L-NAME (group 5) had no significa nt difference in necrosis (68.2 +/- 6.7) versus untreated (group 2) animals . L-Arginine (nitric oxide donor) significantly decreased the severity of m uscle necrosis in this rat model of ischemia-reperfusion injury. L-arginine is known to increase the amount of nitric oxide through the action of nitr ic oxide synthase, whereas L-NAME, known to inhibit nitric oxide synthase a nd decrease nitric oxide production, had comparable results to the untreate d 4-hour ischemia group. These results suggest that L-arginine, presumably through nitric oxide mediation, appears beneficial to rat skeletal muscle s ubjected to ischemia-reperfusion injury.