title: Acidosis induces relaxation mediated by nitric oxide and potassium channels in rat thoracic aorta.
abstract: We investigated the mechanism by which extracellular acidification promotes relaxation in rat thoracic aorta. The relaxation response to HCl-induced extracellular acidification (7.4 to 6.5) was measured in aortic rings pre-contracted with phenylephrine (Phe, 10(-6) M) or KCl (45mM). The vascular reactivity experiments were performed in endothelium-intact and denuded rings, in the presence or absence of indomethacin (10(-5) M), L-NAME (10(-4) M), apamin (10(-6) M), and glibenclamide (10(-5) M). The effect of extracellular acidosis (pH 7.0 and 6.5) on nitric oxide (NO) production was evaluated in isolated endothelial cells loaded with diaminofluorescein-FM diacetate (DAF-FM DA, 5μM). The extracellular acidosis failed to induce any changes in the vascular tone of aortic rings pre-contracted with KCl, however, it caused endothelium-dependent and independent relaxation in rings pre-contracted with Phe. This acidosis induced-relaxation was inhibited by L-NAME, apamin, and glibenclamide, but not by indomethacin. The acidosis (pH 7.0 and 6.5) also promoted a time-dependent increase in the NO production by the isolated endothelial cells. These results suggest that extracellular acidosis promotes vasodilation mediated by NO, K(ATP) and SK(Ca), and maybe other K(+) channels in isolated rat thoracic aorta.
authors.affiliation: Laboratory of Endothelial Function, Department of Surgery and Anatomy, School of Medicine, University of São Paulo, Ribeirão Preto, SP, Brazil. acarla_c@yahoo.com
authors.forename: Andréa C
authors.initials: AC
authors.lastname: Celotto
authors.forename: Carolina B A
authors.initials: CB
authors.lastname: Restini
authors.forename: Verena K
authors.initials: VK
authors.lastname: Capellini
authors.forename: Lusiane M
authors.initials: LM
authors.lastname: Bendhack
authors.forename: Paulo R B
authors.initials: PR
authors.lastname: Evora
mesh_terms: D000138:Acidosis / Q000503:physiopathology*; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005110:Extracellular Space / Q000378:metabolism; D005434:Flow Cytometry; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation
chemical_list: D015221:Potassium Channels; D009569:Nitric Oxide