Hydrogen peroxide-induced vascular relaxation in porcine coronary arteriesis mediated by Ca2+-activated K+ channels

Citation
Y. Hayabuchi et al., Hydrogen peroxide-induced vascular relaxation in porcine coronary arteriesis mediated by Ca2+-activated K+ channels, HEART VESS, 13(1), 1998, pp. 9-17
Citations number
30
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Respiratory Systems
Journal title
HEART AND VESSELS
ISSN journal
0910-8327 → ACNP
Volume
13
Issue
1
Year of publication
1998
Pages
9 - 17
Database
ISI
SICI code
0910-8327(1998)13:1<9:HPVRIP>2.0.ZU;2-U
Abstract
Hydrogen peroxide (H2O2) elicited concentration-dependent relaxation of end othelium-denuded rings of porcine coronary arteries. The relaxation induced by the H2O2 was markedly attenuated by 10 mu M 1H-[1,2,4]oxadiazolo [4,3,a ]quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase, or by 1 00nM charybdotoxin, an inhibitor of large-conductance Ca2+-activated K+ (K- Ca) channels. A combination of the ODQ and charybdotoxin abolished the H2O2 -induced relaxation. Pretreatment with 25 ELM of an Rp stereoisomer of aden osine-3',5'-cyclic monophosphothioate (Rp-cAMPS), 20 mu M glibenclamide, or 1mM 4-aminopyridine did not affect the vascular response to H2O2. The pres ence of catalase at 1000 U/ml significantly attenuated the H2O2-induced rel axation. Exposure of cultured smooth muscle cells to H2O2 activated K-Ca ch annels in a concentration-dependent manner in cell-attached patches. Pretre atment with catalase significantly inhibited the activation of K-Ca channel s. Rp-cAMPS did not inhibit the H2O2-induced activation of K-Ca channels. T he activation of K-Ca channels by H2O2 was markedly decreased in the presen ce of ODQ. However, even in the presence of ODQ, H2O2 activated K-Ca channe ls in a concentration-dependent manner. In inside-out patches, H2O2 signifi cantly activated K-Ca channels through a process independent of cyclic guan osine 3',5'-monophosphate (cGMP). In conclusion, H2O2 elicits vascular rela xation due to activation of K-Ca channels, which is mediated partly by a di rect action on the channel and partly by activation of soluble guanylate cy clase, resulting in the generation of cGMP.