title: In vitro effects of extracellular hypercapnic acidification on the reactivity of rat aorta: Rat aorta vasodilation during hypercapnic acidification.
abstract: The mechanisms by which pH influences vascular tone are not entirely understood, but evidence suggests that the endothelium is involved. Here, we aimed to study the in vitro vascular responses induced by extracellular hypercapnic acidification (HA), as well as the endothelium-dependent mechanisms that are involved in the responses. We bubbled a mixture of CO2(40%)/O2(60%) in an organ bath; we constructed a pH-response curve (pH range 7.4-6.6) and registered isometric force simultaneously. Aortic rings from rats were pre-contracted with phenylephrine (10-6M) and incubated for 30 min in the presence of different chemicals. The relaxations induced by HA occurred in rings with endothelium were: 1) Partially inhibited by indomethacin (10-5M) (PGI2pathway inhibitor); 2) Strongly inhibited by NO pathways: L-NAME (10-4M) and L-NMMA (10-4M) (no specific NO synthase inhibitors); L-Nil (10-3M) (specific iNOS inhibitor); ODQ (10-4M) (specific guanylate cyclase inhibitor), and; 4) Inhibit by tetraethylammonium (10-3M) (non-specific potassium channel inhibitor), glibenclamide (10-5M) (specific KATP inhibitor), aminopyridine (10-3M) (specific Kv inhibitor) and apamin (10-6M) (specific SKCa inhibitor).
  
  
  CONCLUSIONS
  1) HA causes endothelium-dependent relaxation; 2) Indomethacin failed in blocking this relaxation, but the method limitation does not allow ruling out some prostanoid role; 3) The HA vessel relaxation is mediated via cGMP/NO, and; 4) The hyperpolarization occurs by the action of potassium SKCa, KATPand Kvchannels without relying on BKCachannels.
authors.affiliation: Department of Surgery and Anatomy, Ribeirão Preto School of Medicine, University of São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil.
authors.forename: Tales Rubens
authors.initials: TR
authors.lastname: de Nadai
authors.affiliation: Department of Surgery and Anatomy, Ribeirão Preto School of Medicine, University of São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil.
authors.forename: Mariane Nunes
authors.initials: MN
authors.lastname: de Nadai
authors.affiliation: Department of Surgery and Anatomy, Ribeirão Preto School of Medicine, University of São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Cassiano Silveira
authors.affiliation: Department of Surgery and Anatomy, Ribeirão Preto School of Medicine, University of São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil.
authors.forename: Andrea Carla
authors.initials: AC
authors.lastname: Celotto
authors.affiliation: Department of Surgery and Anatomy, Ribeirão Preto School of Medicine, University of São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil.
authors.forename: Agnes Afrodite Sumarelli
authors.initials: AA
authors.lastname: Albuquerque
authors.affiliation: Department of Surgery and Anatomy, Ribeirão Preto School of Medicine, University of São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil.
authors.forename: Marco Tulio Rezende
authors.initials: MT
authors.lastname: de Carvalho
authors.affiliation: Department of Surgery and Anatomy, Ribeirão Preto School of Medicine, University of São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil.
authors.forename: Sandro
authors.initials: S
authors.lastname: Scarpelini
authors.affiliation: Department of Surgery and Anatomy, Ribeirão Preto School of Medicine, University of São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil.
authors.forename: Alfredo José
authors.initials: AJ
authors.lastname: Rodrigues
authors.affiliation: Department of Surgery and Anatomy, Ribeirão Preto School of Medicine, University of São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil. Electronic address: prbevora@gmail.com.
authors.forename: Paulo Roberto Barbosa
authors.initials: PR
authors.lastname: Evora
keywords: Endothelium; Hypercapnic acidification; Nitric oxide; Potassium channels; Prostacyclin; Vascular reactivity