Effect of nitric oxide synthase inhibition on postischemic cerebral hyperemia

We tested the hypothesis that inhibition of nitric oxide synthase (NOS) activity in brain before ischemia decreases postischemic hyperemia. Pentobarbital-anesthetized piglets underwent 15 min of complete global cerebral ischemia induced by elevation of intracranial pressure followed by 20 min of reperfusion. Before ischemia the animals were randomly assigned to receive either intravenous N(ω)-nitro-L-arginine methyl ester (L-NAME 10 mg/kg, n = 6, or 50 mg/kg, n = 6) or an equal volume of saline (10 ml, n = 8). Serial cerebral blood flow (radiolabeled microspheres) was measured at baseline and during ischemia and reperfusion. Forebrain postischemic hyperemia was documented after administration of saline (42 ± 4 to 88 ± 10 ml · min^-1 · 100 g^-1) and 10 mg/kg L-NAME (36 ± 4 to 59 ± 9 ml · min^-1 · 100 g^-1) but not after 50 mg/kg L-NAME (29 ± 3 to 34 ± 7 ml · min^-1 · 100 g^-1). However, the percent reduction in cerebral vascular resistance (CVR) fell during reperfusion to a similar extent in all three groups because of differences between groups in cerebral perfusion pressure changes during the protocol. CVR fell to the lowest level at 8 min of reperfusion in the saline-treated animals (2.0 ± 0.16 to 0.68 ± 0.05 mmHg · ml^-1 · min · 100 g) compared with the L-NAME-treated animals (50 mg/kg: 4.0 ± 0.3 to 1.8 ± 0.2 mmHg · ml^-1 · min · 100 g). Brain NOS activity increased over time in the saline-treated animals (n = 4, maximum 152 ± 29% of baseline at 15 min) but decreased in a dose-related manner after 10 mg/kg (n = 4, 59 ± 27% of baseline at 15 min) and 50 mg/kg L-NAME (n = 5, 10 ± 3% of baseline at 15 min). These results suggest that inhibition of NOS with L-NAME has an effect on early (<8 min) postischemic vasodilation, but it is unlikely that nitric oxide is the sole mediator for postischemic hyperemia beyond 8 min of reperfusion.