l-Arginine-Induced Regional Cerebral Blood Flow Increase is Abolished after Transient Focal Cerebral Ischemia in the Rat

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Abstract
We investigated the l-arginine-induced, regional cerebral blood flow (rCBF) enhancement after different durations of transient focal cerebral ischemia in the rat to determine if l-arginine increases rCBF after transient focal cerebral ischemia. Focal ischemia (5 minutes and 20 minutes) followed by 90 minutes of reperfusion was induced in a normotensive rat suture-model. Regional cerebral blood flow in both hemispheres was measured by laser-Doppler-flowmetry. Reactivity of rCBF to l-arginine (300 mg/kg) was measured 45 minutes after reperfusion, and hypercapnia 90 minutes after reperfusion. The effect of d-arginine and pretreatment with the nitric oxide (NO) synthase inhibitor Nω-nitro-l-arginine (l-NA) (10 mg/kg) was examined in additional groups. Hypercapnia and l-arginine increased rCBF in sham operated controls and on the nonischemic hemispheres. d-arginine did not. Twenty-minute long ischemia significantly reduced the response to l-arginine (control side: 115 ± 5.9%; ischemic side: 107 ± 6.1%, n = 7) and hypercapnia, 5 minutes of ischemia did not. Nω-nitro-l-arginine pretreatment partly restored the l-arginine-induced rCBF increase. Thus, rCBF increase caused by l-arginine in the reperfusion period was unaffected by 5 minutes of ischemia, but reduced by 20 minutes of ischemia. The restoration after pretreatment with l-NA may be caused by attenuated production of cytotoxic substances, e.g., NO and related compounds.