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Vasoconstrictor responses after neo‐intima formation and endothelial removal in the rabbit carotid artery
Author(s) -
Meyer Guido R.Y.,
Bult Hidde,
Üstünes Levent,
Kockx Mark,
Jordaens François H.,
Zonnekeyn Ludo L.,
Herman Arnold G.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb13097.x
Subject(s) - medicine , endothelium , endocrinology , angiotensin ii , nitric oxide , blood vessel , chemistry , blood pressure
1 The present study examined the responses of the rabbit carotid artery to five vasoconstrictors after neo‐intima formation induced by perivascular collar treatment and evaluated the role of constitutive and inducible 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 thromboxanemimetic U‐46619 and 5‐hydroxytryptamine (5‐HT), but not to angiotensin I and II. 3 The collar‐treatment increased the sensitivity to 5‐HT, and decreased the sensitivity to angiotensin II. The sensitivity to U‐46619 and angiotensin I remained unchanged. 4 Mechanical removal of ECs and inhibition of NO biosynthesis by N G ‐monomethyl‐ l ‐arginine ( l ‐NMMA) and N G ‐nitro‐ l ‐arginine ( l ‐NOARG) increased the sensitivity to 5‐HT in sham and collar‐treated segments to the same extent. The effects of collar‐treatment and endothelial removal or treatment with inhibitors of NO biosynthesis were additive. Inhibition of NO biosynthesis failed to augment sensitivity to 5‐HT after endothelial denudation. l ‐NOARG increased the force development to KCl in sham and collar‐treated segments to the same extent. However, l ‐NMMA and l ‐NOARG failed to augment the contractile responses of neo‐intima‐bearing vessels to 5‐HT and KCl after endothelial 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 of the endothelium or incubation with l ‐NOARG counteracted this rightward shift and increased E max . 6 Our results demonstrate that contractions to 5‐HT, angiotensin II and KCl are modulated by NO in both sham and neo‐intima‐bearing vessels. Inhibition of NO biosynthesis and collar treatment resulted in additive effects on the EC 50 values, suggesting that the 5‐HT and angiotensin (AT) receptors on the smooth muscle cells are also modified by the formation of a neo‐intima. Furthermore, the reduced contractile responses of segments with a neo‐intima are not due to NO formed by an inducible NO synthase in those vessels.