Hypoxia-elicited contraction of aorta and coronary artery via removal of endothelium-derived nitric oxide.
To characterize endothelium-derived contracting factor 1 (EDCF1) released under hypoxia, vascular rings isolated from spontaneously hypertensive rat (SHR) aorta and canine coronary artery were suspended for isometric tension recording in an organ chamber filled with a Krebs-Henseleit buffer. In SHR aorta precontracted with norepinephrine (10(-7) M), severe hypoxia induced an initial increase in tension by 36.7 +/- 7.5% followed by a 56.9 +/- 5.7% relaxation; moderate hypoxia induced only a sustained increase in tension by 20.6 +/- 2.5%. Inhibition of nitric oxide (NO) production with N omega-nitro-L-arginine methyl ester (L-NAME) (10(-3) M) augmented norepinephrine-induced precontraction by 76.1 +/- 12.3% and totally eliminated the hypoxic contraction. In canine coronary arteries precontracted with KCl (30 mM) in the presence of indomethacin (10(-5) M), severe hypoxia caused a sustained increase in tension by 68.9 +/- 7.3%, which was also abolished with L-NAME. When L-NAME (10(-3) M) was given after the precontraction, both of these vessels developed sustained contractions under normoxia and moderate hypoxia. These results suggest that the vasocontraction currently considered to be induced by EDCF1 is not caused by a contracting factor but rather is a contracting phenomenon derived from continuous inhibition of basal NO synthesis during hypoxia.
Muramatsu
M
M
Second Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Iwama
Y
Y
Shimizu
K
K
Asano
H
H
Toki
Y
Y
Miyazaki
Y
Y
Okumura
K
K
Hashimoto
H
H
Ito
T
T
D019297:2,4-Dinitrophenol; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D015687:Cell Hypoxia / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D004140:Dinitrophenols / Q000494:pharmacology; D004285:Dogs; D016232:Endothelins / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D010313:Partial Pressure; D051381:Rats; D011918:Rats, Inbred SHR; D012977:Sodium Nitrite / Q000494:pharmacology; D014661:Vasoconstriction
D004140:Dinitrophenols; D016232:Endothelins; D009569:Nitric Oxide; D001120:Arginine; D012977:Sodium Nitrite; D000109:Acetylcholine; D019297:2,4-Dinitrophenol; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine