VASOCONSTRICTOR RESPONSES AFTER NEO-INTIMA FORMATION AND ENDOTHELIAL REMOVAL IN THE RABBIT CAROTID-ARTERY

1 The present study examined the responses of the rabbit carotid arter y to five vasoconstrictors after neo-intima formation induced by periv ascular collar treatment and evaluated the role of constitutive and in ducible nitric oxide (NO) synthase and endothelial cells (ECs). 2 Ring segments of the rabbit carotid artery were mounted in organ chambers for isometric tension recording. Neo-intima-bearing vessels developed less force (E(max)) in response to KCl, the thromboxane-mimetic U-4661 9 and 5-hydroxytryptamine (5-HT), but not to angiotensin I and II. 3 T he collar-treatment increased the sensitivity to 5-HT, and decreased t he sensitivity to angiotensin II. The sensitivity to U-46619 and angio tensin I remained unchanged. 4 Mechanical removal of ECs and inhibitio n of NO biosynthesis by N-G-monomethyl-L-arginine (L-NMMA) and N-G-nit ro-L-arginine (L-NOARG) increased the sensitivity to 5-HT in sham and collar-treated segments to the same extent. The effects of collar-trea tment and endothelial removal or treatment with inhibitors of NO biosy nthesis were additive. Inhibition of NO biosynthesis failed to augment sensitivity to 5-HT after endothelial denudation. L-NOARG increased t he force development to KCl in sham and collar-treated segments to the same extent. However, L-NMMA and L-NOARG failed to augment the contra ctile responses of neo-intima-bearing vessels to 5-HT and KCl after en dothelial removal. 5 The responses to angiotensin I were not altered, either by the neo-intima or by endothelial removal. In arteries with a neo-intima the sensitivity to angiotensin II was decreased. Removal o f the endothelium or incubation with L-NOARG counteracted this rightwa rd shift and increased E(max). 6 Our results demonstrate that contract ions to 5-HT, angiotensin II and KCl are modulated by NO in both sham and neo-intima-bearing vessels. Inhibition of NO biosynthesis and coll ar treatment resulted in additive effects on the EC(50) values, sugges ting that the 5-HT and angiotension (AT) receptors on the smooth muscl e cells are also modified by the formation of a neo-intima. Furthermor e, the reduced contractile responses of segments with a neo-intima are not due to NO formed by an inducible NO synthase in those vessels.