© 2000 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Different Vasculoprotective Roles of NO Synthase Isoforms in Vascular Lesion Formation in Mice
Presented in part at the 72nd Scientific Sessions of the American Heart Association, Atlanta, Ga, November 7–10, 1999.
From the Department of Cardiovascular Medicine (K.Y., H.S., H.F., T.K., K.M., K.E., A.T.), Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; the Department of Microbiology (S.O., T.A.), Kumamoto University School of Medicine, Kumamoto, Japan; and the Cardiovascular Center (P.H.), Massachusetts General Hospital, Harvard Medical School, Boston, Mass.
Correspondence to Hiroaki Shimokawa, MD, PhD, Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. E-mail shimo{at}cardiol.med.kyushu-u.ac.jp
Abstract—NO is known to have several important vasculoprotective actions. Although NO is synthesized by 3 different NO synthase (NOS) isoforms, the vasculoprotective action of individual NOS isoforms remains to be clarified. Permanent ligation of the left common carotid artery was performed in control, endothelial NOS (eNOS) knockout (eNOS-KO), and inducible NOS (iNOS) knockout (iNOS-KO) mice. Four weeks after the procedure, neointimal formation and reduction of cross-sectional vascular area (constrictive remodeling) were noted in the left carotid artery. In the eNOS-KO mice, the extent of neointimal formation was significantly larger than in the control or iNOS-KO mice, whereas the extent of vascular remodeling was the highest in the iNOS-KO mice compared with other 2 strains. Antiplatelet therapy with aspirin or antihypertensive treatment with bunazosin failed to inhibit the accelerated neointimal formation in the eNOS-KO mice. These results indicate that eNOS and iNOS have different vasculoprotective actions against the vascular lesion formation caused by blood flow disruption in vivo: NO derived from eNOS inhibits neointimal formation, whereas NO derived from iNOS suppresses the development of constrictive remodeling.
Key Words: nitric oxide • nitric oxide synthase • arteriosclerosis • neointimal formation • vascular remodeling
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