ENDOTHELIAL PROSTANOIDS INVOLVED IN THE RELAXATION PRODUCED BY ACETYLCHOLINE IN THE HUMAN PULMONARY-ARTERY

In ring preparations of human pulmonary artery contracted with noradre naline (NA), the application of acetylcholine (ACh) enhanced the tensi on, and withdrawal produced a large relaxation which was sustained for about 10 min and required over 20 min for recovery; the latter relaxa tion appeared only in the endothelium-intact preparation. Indomethacin increased the amplitude of NA contractions, changed the ACh-induced c ontraction to relaxation, and inhibited the ACh-induced sustained rela xation. Nitroarginine increased the amplitude of NA and ACh-induced co ntractions, with no significant change in the ACh-induced sustained re laxation. These effects of indomethacin and nitroarginine were observe d only in the endothelium-intact preparations. In NA-contracted prepar ations, exogenously applied prostaglandin I-2 (PGI(2)) produced relaxa tion. Thus, in human pulmonary arteries, NA and ACh activities release vasodilator prostanoids and nitroarginine-sensitive EDRF from the end othelium, and initiate direct contractile actions to smooth muscle. Th e prostanoid-induced relaxation is sustained for a long time after the withdrawal of ACh stimulation and can be mimicked by exogenously-appl ied PGI(2).