Chronic carbon monoxide exposure of hypoxic rats increases in vitro sensitivity of pulmonary artery smooth muscle.
Exogenous carbon monoxide (CO) induces pulmonary vasodilation by acting directly on pulmonary artery (PA) smooth muscle cells. We investigated the contribution of K+ channels and soluble guanylyl cyclase to the regulation of PA tone by acute CO in chronic hypoxic rats (3 weeks at 0.5 atm (1 atm = 101.325 kPa); hypoxic) and in chronic hypoxic rats exposed to exogenous CO (3 weeks at 0.5 atm + 50 ppm CO; hypoxic-CO). Acute CO induced relaxation in PA rings from all animals. However, the amplitude of CO relaxation was significantly decreased in hypoxic rings and increased in hypoxic-CO rings. This different effect occurred with a decrease and an increase of pD2, respectively, in hypoxic and hypoxic-CO rings. We showed a positive relation between the percentage of inhibition of CO relaxation by a blocker of K+ channels and the increase of CO sensitivity. Thus, we showed for the first time that chronic hypoxia decreases acute CO sensitivity, which in contrast, increases in the presence of chronic CO. The present study provides initial evidence of a link between increased K(+)-channel activity and CO sensitivity.
Dubuis
Eric
E
Laboratoire de physiopathologie de la paroi artérielle (LABPART), Institut Fédératif de Recherche no 120, Faculté de Médecine, 2 bis, boulevard Tonnellé, 37032 Tours, France.
Gautier
Mathieu
M
Melin
Alexandre
A
Rebocho
Manuel
M
Girardin
Catherine
C
Bonnet
Pierre
P
Vandier
Christophe
C
D000818:Animals; D002248:Carbon Monoxide / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D002248:Carbon Monoxide