L-ARGININE DOES NOT IMPROVE CORTICAL PERFUSION OR HISTOPATHOLOGICAL OUTCOME IN SPONTANEOUSLY HYPERTENSIVE RATS SUBJECTED TO DISTAL MIDDLE CEREBRAL-ARTERY PHOTOTHROMBOTIC OCCLUSION

The potential of nitric oxide (NO) to influence positively or negative ly the outcome of mechanically induced focal cerebral ischemia is stil l controversial. Recent evidence suggests that NO of vascular origin, whether synthesized from exogenously administered L-arginine (L-Arg) o r from NO donor compounds, is beneficial but that of neuronal origin i s not. However, the therapeutic potential of NO to ameliorate stroke i nduced by arterial thrombosis has not been reported. We assessed the t herapeutic effect of L-Arg administration in spontaneously hypertensiv e rats (SHR) subjected to permanent photo-thrombotic occlusion of the distal middle cerebral artery (dMCA). The ipsilateral carotid artery w as left unligated to enhance L-Arg delivery into the putative penumbra l region. Local CBF (LCBF) was assessed at 30 min by the [C-14]iodoant ipyrine technique (n = 9), while histological infarct volumes and inde x of peripheral ischemic cell change were determined at 3 days (n = 7) . Rats (n = 9) given 300 mg/kg L-Arg at 18 and 3 h before photothrombo tic dMCA occlusion and at 5 min afterward displayed no significant dif ferences in LCBF compared with animals (n = 8) injected with water (th e carrier vehicle) and similarly irradiated, Infarct volumes were also similar, being 37.0 +/- 9.7 mm(3) (SD) in the vehicle-treated and 49. 1 +/- 17.2 mm(3) (SD) in the L-Arg-treated groups (both n = 7), as wer e assessments of ischemic neuronal density in the penumbra. In contras t, L-Arg administered intravenously in a dose of 300 mg/kg to nonische mic SHR (n = 5) increased cortical CBF by similar to 75% during a 70-m in observation period. We conclude that thrombotic processes superimpo sed upon cerebral ischemia may facilitate tissue reactions that offset the potentially beneficial effect of L-Arg, and this caveat must be c onsidered when proposing L-Arg for clinical treatment of focal thrombo tic stroke.