Inhibition of hypoxic pulmonary vasoconstriction of rats by carbon monoxide.
Hypoxic pulmonary vasoconstriction (HPV), a unique response of pulmonary circulation, is critical to prevent hypoxemia under local hypoventilation. Hypoxic inhibition of K(+) channel is known as an important O(2)-sensing mechanism in HPV. Carbon monoxide (CO) is suggested as a positive regulator of Ca(2+)-activated K(+) channel (BK(Ca)), a stimulator of guanylate cyclase, and an O(2)-mimetic agent in heme moiety-dependent O(2) sensing mechanisms. Here we compared the effects of CO on the HPV (P(O(2)), 3%) in isolated pulmonary artery (HPV(PA)) and in blood-perfused/ventilated lungs (HPV(lung)) of rats. A pretreatment with CO (3%) abolished the HPV(PA) in a reversible manner. The inhibition of HPV(PA) was completely reversed by 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), a guanylate cyclase inhibitor. In contrast, the HPV(lung) was only partly decreased by CO. Moreover, the partial inhibition of HPV(lung) by CO was affected neither by the pretreatment with ODQ nor by NO synthase inhibitor (L-NAME). The CO-induced inhibitions of HPV(PA) and HPV(lung) were commonly unaffected by tetraethylammonium (TEA, 2 mM), a blocker of BK(Ca). As a whole, CO inhibits HPV(PA) via activating guanylate cyclase. The inconsistent effects of ODQ on HPV(PA) and HPV(lung) suggest that ODQ may lose its sGC inhibitory action when applied to the blood-containing perfusate.
Yoo
Hae Young
HY
Department of Physiology, Seoul National University College of Medicine, Seoul, Korea.
Park
Su Jung
SJ
Bahk
Jae Hyon
JH
Kim
Sung Joon
SJ
D000818:Animals; D002248:Carbon Monoxide / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000860:Hypoxia / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester / Q000737:chemistry / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010069:Oxadiazoles / Q000737:chemistry / Q000494:pharmacology; D011651:Pulmonary Artery / Q000503:physiopathology*; D011810:Quinoxalines / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D019789:Tetraethylammonium / Q000737:chemistry / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D010069:Oxadiazoles; D011810:Quinoxalines; D019789:Tetraethylammonium; D002248:Carbon Monoxide; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D019331:NG-Nitroarginine Methyl Ester