Article date: May 1999
By: Sophie Parmentier, Georg Andrees Böhme, Dominique Lerouet, Dominique Damour, Jean‐Marie Stutzmann, Isabelle Margaill, Michel Plotkine, in Volume 127, Issue 2, pages 546-552
The aim of this study was to investigate the effect of N‐(3‐(aminomethyl)benzyl)acetamidine (1400W), a selective inhibitor of inducible calcium‐independent nitric oxide synthase (iNOS), on the functional and histopathological outcomes of experimental transient focal cerebral ischaemia in rats.
Transient ischaemia was produced by the occlusion for 2 h of both the left middle cerebral artery and common carotid artery. Treatments with 1400W (20 mg kg−1) or vehicle were started 18 h after occlusion of the arteries and consisted in seven subcutaneous injections at 8 h interval. Ischaemic outcomes and NOS activities (constitutive and calcium‐independent NOS) were evaluated 3 days after ischaemia.
1400W significantly reduced ischaemic lesion volume by 31%, and attenuated weight loss and neurological dysfunction.
1400W attenuated the calcium‐independent NOS activity in the infarct by 36% without affecting the constitutive NOS activity.
These findings suggest that iNOS activation contributes to tissue damage and that selective inhibitors of this isoform may be of interest for the treatment of stroke.
The aim of this study was to investigate the effect of N‐(3‐(aminomethyl)benzyl)acetamidine (1400W), a selective inhibitor of inducible calcium‐independent nitric oxide synthase (iNOS), on the functional and histopathological outcomes of experimental transient focal cerebral ischaemia in rats.
Transient ischaemia was produced by the occlusion for 2 h of both the left middle cerebral artery and common carotid artery. Treatments with 1400W (20 mg kg−1) or vehicle were started 18 h after occlusion of the arteries and consisted in seven subcutaneous injections at 8 h interval. Ischaemic outcomes and NOS activities (constitutive and calcium‐independent NOS) were evaluated 3 days after ischaemia.
1400W significantly reduced ischaemic lesion volume by 31%, and attenuated weight loss and neurological dysfunction.
1400W attenuated the calcium‐independent NOS activity in the infarct by 36% without affecting the constitutive NOS activity.
These findings suggest that iNOS activation contributes to tissue damage and that selective inhibitors of this isoform may be of interest for the treatment of stroke.
British Journal of Pharmacology (1999) 127, 546–552; doi:10.1038/sj.bjp.0702549
DOI: 10.1038/sj.bjp.0702549
View this article