[The role of endothelium-derived contracting factor (EDCF) and endothelium-derived relaxing factor (EDRF) in the aorta of the rat: identification of EDCF].
The present experiment was performed to identify endothelium-derived contracting factor produced by acetylcholine stimulation in the aorta of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). The rings of the thoracic aorta were obtained from age-matched SHR and WKY, and changes in isometric tension were recorded. The relaxant responses to acetylcholine in the rings from SHR were significantly weaker than those obtained in WKY. The relaxant responses to acetylcholine were significantly enhanced by pretreatment with a cyclooxygenase-inhibitor (indomethacin) or thromboxane A2/prostaglandin H2 receptor antagonist (ONO-3708) both in the SHR and WKY rings. A thromboxane A2 synthetase inhibitor (OKY-046) did not affect the acetylcholine-induced relaxation in the rings from SHR or WKY. In the organ bath solution, following acetylcholine stimulation, prostaglandin E2 and 6-keto-prostaglandin F1 alpha concentrations increased, but prostaglandin F2 alpha and thromboxane B2 concentrations did not increase. Exogenous prostaglandin H2, a stable analogue of thromboxane A2 (STA2) and prostaglandin F2 alpha induced contractions of the SHR rings at a lower concentration than prostaglandin E2, prostaglandin D2 and prostaglandin I2. These contractile responses to various prostaglandins were markedly inhibited by pretreatment with ONO-3708. A prostacyclin synthetase inhibitor did not affect the relaxant responses to acetylcholine in the SHR rings. These results show that endothelium-derived contracting factor is produced and released by acetylcholine stimulation not only in the aorta of SHR but also in that of WKY. The results also suggest that prostaglandin H2, a precursor of the released prostaglandins, is a strong candidate for endothelium-derived contracting factor produced by acetylcholine stimulation.
Ito
T
T
2nd Department of Internal Medicine, Nagoya University School of Medicine.
Kato
T
T
Iwama
Y
Y
Muramatsu
M
M
Okumura
K
K
Hashimoto
H
H
Satake
T
T
Ogawa
K
K
D000818:Animals; D001013:Aorta, Thoracic; D016232:Endothelins / Q000096:biosynthesis / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D016232:Endothelins; D009569:Nitric Oxide