Endothelial Prostanoids Involved in the Relaxation Produced by Acetylcholine in the Human Pulmonary Artery.

Abstract

In ring preparations of human pulmonary artery contracted with noradrenaline (NA), the application of acetylcholine (ACh) enhanced the tension, and withdrawal produced a large relaxation which was sustained for about 10 min and required over 20 min for recovery; the latter relaxation appeared only in the endothelium-intact preparation. Indomethacin increased the amplitude of NA contractions, changed the ACh-induced contraction to relaxation, and inhibited the ACh-induced sustained relaxation. Nitroarginine increased the amplitude of NA and ACh-induced contractions, with no significant change in the ACh-induced sustained relaxation. These effects of indomethacin and nitroarginine were observed only in the endothelium-intact preparations. In NA-contracted preparations, exogenously applied prostaglandin I2 (PGI2) produced relaxation. Thus, in human pulmonary arteries, NA and ACh activities release vasodilator prostanoids and nitroarginine-sensitive EDRF from the endothelium, and initiate direct contractile actions to smooth muscle. The prostanoid-induced relaxation is sustained for a long time after the withdrawal of ACh stimulation and can be mimicked by exogenously-applied PGI2.