Evidence for NO involvement in regulating vascular reactivity in balloon-injured rat carotid artery

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 (NO). Balloon injury was performed using a 2-F Fogarty catheter. After 2 and 4 wk, 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 (ANG II), endothelin-1, and serotonin were all attenuated in the injured vessels compared with the uninjured carotid arteries [0.38 +/- 0.11 vs. 0.73 +/- 0.10 g (n = 5), norepinephrine; 0.15 +/- 0.06 vs. 0.38 +/- 0.05 g (n = 4), ANG II; 0.60 +/- 0.14 vs. 1.05 +/- 0.12 g (n = 4), endothelin-1; 0.23 +/- 0.07 vs. 0.60 +/- 0.06 g (n = 12), serotonin]. Contractile responses induced by KCl were not affected by the balloon injury (0.62 +/- 0.10 vs. 0.64 +/- 0.09 g, n = 4). Interestingly, carbachol, a muscarinic agonist and vasodilator, caused concentration-dependent relaxations in 2- as well as 4-wk postinjured vessels despite the absence of endothelium. The NO synthase inhibitors, N omega-L-arginine methyl ester (L-NAME) and N omega-nitro-L-arginine (L-NNA), 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.(ABSTRACT TRUNCATED AT 250 WORDS)