Age-related endothelium-dependent vascular relaxation in rat thoracic aorta in response to colforsin

Citation
K. Mori et al., Age-related endothelium-dependent vascular relaxation in rat thoracic aorta in response to colforsin, PEDIATR INT, 41(6), 1999, pp. 673-681
Citations number
21
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pediatrics
Journal title
PEDIATRICS INTERNATIONAL
ISSN journal
1328-8067 → ACNP
Volume
41
Issue
6
Year of publication
1999
Pages
673 - 681
Database
ISI
SICI code
1328-8067(199912)41:6<673:AEVRIR>2.0.ZU;2-4
Abstract
Background: Colforsin, a novel water-soluble forskolin derivative, increase s intracellular cyclic AMP by direct stimulation of adenylate cyclase and h as strong positive inotropic and vasodilative effects. However, it is not k nown whether colforsin causes nitric oxide (NO) release and enhances endoth elium-dependent vascular relaxation. Methods: We studied NO production and relaxation on exposure to colforsin i n thoracic aorta from rats aged 4, 12 and 60 weeks. Results: When a low concentration of colforsin was added to a solution bath ing ring segments of aorta from 12-week-old rats, relaxation was greater in the ring segments with intact endothelium than in those from which the end othelium had been removed. A high concentration of colforsin induced the sa me degree of relaxation of ring segments with or without endothelium, proba bly by a direct effect on vascular smooth muscle cells. Production of NO in response to colforsin by cultured endothelial cells from 12-week-old rat a orta was demonstrated by the electron paramagnetic resonance spin trapping method. A low concentration of colforsin relaxed aortic segments with intac t endothelium from 4-week-old rats more than those from 12-week-old or 60-w eek-old rats. Reversal of relaxation by N-G-nitro L-arginine, an NO synthes is inhibitor, was most significant in arteries from 4-week-old rats. Produc tion of NO after exposure to colforsin was greater in aortic segments from 4-week-old rats than older rats, as detected by an NO-selective electrode. Conclusions: Colforsin induces vasodilation in part by releasing NO from th e endothelium in rat thoracic aorta. In addition to a direct vasodilative e ffect on the vascular smooth muscle cells, an endothelium-dependent vasodil ative effect is also important in younger arteries.