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. These data indicate that balloon angioplasty induces the formation of NO in the vessel wall and that NO may be important in maintaining an adequate tissue perfusion in the balloon-injured artery by attenuating vasoconstrictor activity in an already structurally compromised vessel.