Nitric oxide donors increase blood flow and reduce brain damage in focal ischemia: evidence that nitric oxide is beneficial in the early stages of cerebral ischemia - PubMed (original) (raw)

Nitric oxide donors increase blood flow and reduce brain damage in focal ischemia: evidence that nitric oxide is beneficial in the early stages of cerebral ischemia

F Zhang et al. J Cereb Blood Flow Metab. 1994 Mar.

Abstract

We studied whether administration of nitric oxide (NO) donors reduces the ischemic damage resulting from middle cerebral artery (MCA) occlusion in spontaneously hypertensive rats (SHRs). In halothane-anesthetized and ventilated SHRs, the MCA was occluded. CBF was monitored using a laser-Doppler flowmeter. Three to five minutes after MCA occlusion, the NO donors sodium nitroprusside (SNP; 3 mg/kg/h) or 3-morpholino-sydnonimine (SIN 1; 1.5-6 mg/kg/h) were administered into the carotid artery for 60 min. As a control, the effect of papaverine (3.6 mg/kg/h), a vasodilator that acts independently of NO, was also studied. The hypotension evoked by these agents was counteracted by intravenous infusion of phenylephrine. At the end of the infusion, rats were allowed to recover. Stroke size was determined 24 h later in thionin-stained sections. In sham occluded rats, SNP (n = 5), SIN 1 (n = 5), and papaverine (n = 5) produced comparable increases in CBF (p > 0.05 from vehicle). After MCA occlusion, SNP (n = 5) and SIN 1 (n = 5), but not papaverine (n = 5), enhanced the recovery of CBF (p < 0.05 from vehicle) and reduced the size of the infarct by 28 +/- 12 and 32 +/- 7%, respectively (mean +/- SD; p < 0.05 from vehicle). To determine whether NO donors could act by inhibiting platelet aggregation, we studied the effect of SNP on collagen-induced platelet aggregation. Intracarotid administration of SNP (3 mg/kg/h for 60 min) did not affect platelet aggregation to collagen, suggesting that the protective effect of NO donors was not due to inhibition of platelet function. We conclude that NO donors increase CBF to the ischemic territory and reduce the tissue damage resulting from focal ischemia. The protective effect may result from an increase in CBF to the ischemic territory, probably the ischemic penumbra. These findings suggest that NO donors may represent a new therapeutic strategy for the management of acute stroke.

PubMed Disclaimer

Cited by

Cilostazol, a phosphodiesterase inhibitor, attenuates photothrombotic focal ischemic brain injury in hypertensive rats.
Ito H, Hashimoto A, Matsumoto Y, Yao H, Miyakoda G. Ito H, et al. J Cereb Blood Flow Metab. 2010 Feb;30(2):343-51. doi: 10.1038/jcbfm.2009.220. Epub 2009 Oct 7. J Cereb Blood Flow Metab. 2010. PMID: 19809463 Free PMC article.
Increased susceptibility to ischemic brain damage in transgenic mice overexpressing the amyloid precursor protein.
Zhang F, Eckman C, Younkin S, Hsiao KK, Iadecola C. Zhang F, et al. J Neurosci. 1997 Oct 15;17(20):7655-61. doi: 10.1523/JNEUROSCI.17-20-07655.1997. J Neurosci. 1997. PMID: 9315887 Free PMC article.
Responses to Cortical Spreading Depression under Oxygen Deficiency.
Sonn J, Mayevsky A. Sonn J, et al. Open Neurol J. 2012;6:6-17. doi: 10.2174/1874205X01206010006. Epub 2012 Apr 27. Open Neurol J. 2012. PMID: 22670162 Free PMC article.
Long-term elevation of cyclooxygenase-2, but not lipoxygenase, in regions synaptically distant from spreading depression.
Caggiano AO, Breder CD, Kraig RP. Caggiano AO, et al. J Comp Neurol. 1996 Dec 16;376(3):447-62. doi: 10.1002/(SICI)1096-9861(19961216)376:3<447::AID-CNE7>3.0.CO;2-2. J Comp Neurol. 1996. PMID: 8956110 Free PMC article.
Ameliorating effects of Kangen-karyu on neuronal damage in rats subjected to repeated cerebral ischemia.
Pu F, Kaneko T, Enoki M, Irie K, Okamoto T, Sei Y, Egashira N, Oishi R, Mishima K, Kamimura H, Iwasaki K, Fujiwara M. Pu F, et al. J Nat Med. 2010 Apr;64(2):167-74. doi: 10.1007/s11418-010-0392-y. Epub 2010 Feb 13. J Nat Med. 2010. PMID: 20155403

Nitric oxide donors increase blood flow and reduce brain damage in focal ischemia: evidence that nitric oxide is beneficial in the early stages of cerebral ischemia - PubMed (original) (raw)