Evidence for nitric oxide involvement in regulating vascular reactivity in the balloon-injured rat carotid artery. Major, Terry C., Ronald W. Overhiser, and Robert L. Panek. Department of Therapeutics, Cardiovascular Section, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, 2800 Plymouth Road, Ann Arbor, MI 48105
APStracts 2:0123H, 1995.
The present study evaluated the influence of this newly formed intima on vascular reactivity in balloon- injured carotid arteries and the regulatory role of the vasodilator, nitric oxide. Balloon injury was performed using a 2F Fogarty catheter. After 2 and 4 weeks, carotid artery segments were removed for both histomorphometric analysis and determination of in vitro contractile responses. Histomorphometric analysis showed a marked intimal thickening with an intima to media ratio of 126 + 19% (n=5). The lack of factor VIII staining in injured carotid arteries revealed the absence of endothelium since factor VIII-related antigen is a glycoprotein synthesized by endothelial cells. Functionally, maximal contractile responses to norepinephrine, angiotensin II, endothelin-1 and serotonin were all attenuated in the injured vessels compared to the uninjured carotid arteries (0.38 + 0.11 vs 0.73 + 0.10g (n=5), norepinephrine; 0.15 + 0.06 vs 0.38 + 0.05g (n=4), angiotensin II; 0.60 + 0.14 vs 1.05 + 0.12g (n=4), endothelin-1 and 0.23 + 0.07 vs 0.60 + 0.06g (n=12), serotonin). Contractile responses induced by KCl were not affected by the balloon injury (0.62 + 0.10 vs 0.64 + 0.09g, n=4). Interestingly, carbachol, a muscarinic agonist and vasodilator, caused concentration-dependent relaxations in 2 as well as 4 week post injured vessels despite the absence of endothelium. The nitric oxide synthase inhibitors, Nw-L -arginine methyl ester (L-NAME) and Nw-nitro-L-arginine (L-NA), blocked the relaxation responses evoked by carbachol. Exogenously administered L-arginine reversed this blockade of the NOS inhibitors on the carbachol-induced relaxations. In addition, L-NAME partially reversed in a concentration-dependent manner the reduced maximal contractile force elicited by serotonin in the injured carotid artery. These data indicate that balloon angioplasty induces the formation of nitric oxide in the vessel wall and that nitric oxide may be important in maintaining an adequate tissue perfusion in the balloon-injured artery by attenuating vasoconstrictor activity in an already structurally compromised vessel. 

Received 6 February 1995; accepted in final form 23 March 1995.
APS Manuscript Number H113-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on  4 April 1995.