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 neuroprotective effects of two NO donors, the classical nitrovasodilator sodium nitroprusside (SNP) and the NONOate spermine/NO, after transient focal cerebral ischemia in rats. Parietal cortical perfusion was measured by laser-Doppler flowmetry. The effects of increasing intravenous doses (10-300 microgram) of sodium nitroprusside and spermine/NO on cortical perfusion and arterial blood pressure were assessed. Transient (2 h) focal cerebral ischemia was carried out by the intraluminal thread method. The effects of intraischemic intravenous 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 reperfusion were assessed. In control conditions, SNP and, to a lesser extent, spermine/NO induced dose-dependent hypotension and concomitant reduction in cortical perfusion. In focal cerebral ischemia, infusion of SNP (0.11 mg/kg) and spermine/NO (0.36, 3.6 mg/kg) reduced the infarct size. In the case of spermine/NO, cortical perfusion was maintained above the control levels during the ischemic insult. No significant hypotension was elicited by NO donors at the dose-ratios infused. In conclusion, brain damage induced by transient focal ischemia is reduced by intravenous NO donors. Neuroprotective effects of spermine/NO are due at least in part to improvement of brain perfusion, while sodium nitroprusside must provide direct cytoprotection. These results give further support to the protective effect of NO in the early stages of cerebral ischemia and point to the therapeutic potential of NONOates in the management of brain ischemic damage.
Salom
J B
JB
Centro de Investigación, Hospital Universitario La Fe, Universidad de Valencia, Ave. Campanar 21, E46009, Valencia, Spain. salom_iba@gva.es
Ortí
M
M
Centeno
J M
JM
Torregrosa
G
G
Alborch
E
E
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000098:blood supply / Q000187:drug effects; D002544:Cerebral Infarction / Q000188:drug therapy*; D002546:Ischemic Attack, Transient / Q000188:drug therapy; D008297:Male; D020030:Nitric Oxide Donors / Q000494:pharmacology / Q000627:therapeutic use*; D009599:Nitroprusside / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013096:Spermine / Q000494:pharmacology / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*
D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D009599:Nitroprusside; D013096:Spermine