Mechanisms of vascular preservation by a novel no donor following rat carotid artery intimal injury. Guo, Jin-Ping, Manoj M. Panday, P. Macke Consigny, and Allan M. Lefer. Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, U.S.A.
APStracts 2:0135H, 1995.
We studied the effects of a novel organic nitric oxide donor, CAS 1609, in a rat carotid artery intimal injury model. The NO donor, CAS 1609, or its non-NO donating control compound, C93-4845, were infused intravenously at 30 [mu]g/day. Seven days after injury, carotid artery rings contracted only 56+/-6 mg to L-NAME in C93-4845 treated rats, compared with 120+/-17 mg in CAS 1609 treated rats (p<0.02), indicating a preservation of endogenous NO release. Improved responses to the endothelium-dependent dilator, acetylcholine also occurred in injured arteries treated with CAS 1609. Morphometric analysis of injured carotid arteries given the inactive compound showed marked intimal thickening with an intimal/medial (I/M) ratio of 0.76+/-0.02, compared with a significantly lower I/M ratio of 0.32+/-0.04 (p<0.01) in injured carotid arteries given CAS 1609. Additionally, CAS 1609 was found to have a concentration-dependent stimulatory effect on cultured rat aortic endothelial cell proliferation (p<0.01), but an inhibitory effect on PDGF-BB (10 ng/ml) stimulated rat aortic smooth muscle cell proliferation (p<0.01). This is the first study to demonstrate that NO plays a dual role in vascular cell proliferation, stimulating endothelial cells, but inhibiting smooth muscle cell proliferation. This dual effect of NO on cell proliferation is associated with an in vivo reduction in neointimal thickening and an acceleration of endothelial recovery determined by both anatomic and functional methods. 

Received 29 December 1994; accepted in final form 31 March 1995.
APS Manuscript Number H1145-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 19 April 1995.