Nitric Oxide and the Pulmonary Circulation in the Adult

Abstract

Despite its very potent vasodilating action in vivo, acetylcholine does not always produce vasorelaxation in isolated blood vessel preparations (Furchgott and Bhadrakom 1953; Furchgott 1955). In 1980 Furchgott and Zawadski reported that the relaxing effect of acetylcholine on isolated arteries was dependent upon the presence of the vascular endothelium (Furchgott and Zawadzki 1980). They also suggested that the relaxing effect of acetylcholine was mediated by an unstable humoral factor, later named endothelium-dependent relaxing factor (EDRF) (Furchgott 1984, Martin et al. 1986). On the basis of the similar pharmacological responses of EDRF and nitric oxide (NO), two research groups independently published results in 1987 suggesting that NO accounts for the action of EDRF (Furchgott 1988; Ignarro et al. 1988). Further studies in vascular strips and platelets demonstrated that the activities of EDRF and NO were largely indistinguishable (Furchgott 1984; Griffith et al. 1984; Ignarro et al. 1987a,b). The similarity was finally confirmed, although questioned by others (Myers et al. 1990). Until recently, NO was discussed only for its contribution to environmental pollution, e. g., as an internal combustion engine pollutant, and in formation of smog and acid rain. However, from its apparent widespread distribution in mam malian biology (Nathan 1992), NO played an important role in the evolution of living systems (Anbar 1996). Nitric oxide was honored by receiving the title of “Molecule of the Yea” in 1992 (Culotta and Koshland 1992).