[Mechanism of constriction and dilatation of pulmonary artery induced by hydrogen peroxide].
Hydrogen peroxide (H2O2) is known to cause transient pulmonary vasoconstriction in isolated lungs perfused with a solution containing no blood components, by inducing vasoactive arachidonate metabolites such as thromboxane A2 (TXA2). However, the exact site of production of the vasoactive arachidonates in the lung tissue is unclear. Using isolated main pulmonary arterial rings obtained from male Sprague-Dawley rats (B.W. 300-350 g), we attempted to examine the arachidonate metabolism, especially that mediated by cyclooxygenase, in the vascular wall of pulmonary artery without endothelium. Changes in isometric tension were used to measure contraction or dilatation of the ring preparation. H2O2 caused transient contraction of the ring, which was treated previously with a solution containing a high concentration of potassium (20 mM). The contractile response was enhanced in parallel with the concentration of H2O2 in the presence or absence of endothelium. Catalase (1000 U/ml), a H2O2 scavenger, completely inhibited the response of the isolated ring (without endothelium) to H2O2. OKY-046 (10(-5) and 10(-4) M), a TXA2 synthetase blocker, partially attenuated the contractile response induced by H2O2. ONO-3708 (10(-5) M), a TXA2 and prostaglandin H2 receptor blocker, fully inhibited the vasoconstriction and caused relaxation of the ring without endothelium after addition of H2O2. Indomethacin (5 microM), a cyclooxygenase inactivator, completely inhibited both vasoconstriction and vasodilation of the denuded ring. H2O2 also induced the release of 6-keto-prostaglandin F1 alpha, a stable metabolite of the vasodilator, prostacyclin, from the pulmonary artery without endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)
Asano
K
K
Department of Medicine, School of Medicine, Keio University, Tokyo, Japan.
Yamaguchi
K
K
Kawai
A
A
Mori
M
M
Takasugi
T
T
Umeda
A
A
Kawashiro
T
T
D000818:Animals; D011464:Epoprostenol / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D044262:Prostaglandin H2; D011463:Prostaglandins H / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013928:Thromboxane A2 / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D011463:Prostaglandins H; D044262:Prostaglandin H2; D013928:Thromboxane A2; D006861:Hydrogen Peroxide; D011464:Epoprostenol