Reduction of infarct size by the NO donors sodium nitroprusside and spermine/NO after transient focal cerebral ischemia in rats

Nitric oxide (NO) plays a dual role (neuroprotection and neurotoxicity) in cerebral ischemia. NO promoting strategies may be beneficial shortly after ischemia. Therefore, we have studied the hemodynamic and possible neuroprot ective effects of two NO donors, the classical nitrovasodilator sodium nitr oprusside (SNP) and the NONOate spermine/NO, after transient focal cerebral ischemia in rats. Parietal cortical perfusion was measured by laser-Dopple r flowmetry. The effects of increasing intravenous doses (10-300 mu g) of s odium nitroprusside and spenmine/NO on cortical perfusion and arterial bloo d pressure were assessed. Transient (2 h) focal cerebral ischemia was carri ed out by the intraluminal thread method. The effects of intraischemic intr avenous infusion of SNP (0.11, 1.1 mg/kg) and spermine/NO (0.36, 3.6 mg/kg) on hemodynamic parameters and infarct size developed after 1 week reperfus ion were assessed. In control conditions, SNP and, to a lesser extent, sper mine/NO induced dose-dependent hypotension and concomitant reduction in cor tical perfusion. In focal cerebral ischemia, infusion of SNP (0.11 mg/kg) a nd spermine/NO (0.36, 3.6 mg/kg) reduced the infarct size. In the case of s permine/NO, cortical perfusion was maintained above the control levels duri ng the ischemic insult. No significant hypotension was elicited by NO donor s at the dose-ratios infused. In conclusion, brain damage induced by transi ent focal ischemia is reduced by intravenous NO donors. Neuroprotective eff ects of spermine/NO are due at least in part to improvement of brain perfus ion, while sodium nitroprusside must provide direct cytoprotection. These r esults give further support to the protective effect of NO in the early sta ges of cerebral ischemia and point to the therapeutic potential of NONOates in the management of brain ischemic damage. (C) 2000 Published by Elsevier Science BN. All rights reserved.