Noboru Toda

Nitric Oxide Derived from Perivascular Nerves and Endothelium

Endothelium-derived relaxing factor (EDRF) was discovered by Furchgott and Zawadzki (1980), who observed that acetylcholine-induced relaxation of the isolated rabbit aorta was endothelium-dependent and that vascular smooth muscle directly responded to acetylcholine with slight contraction. The discovery brought us the marvelous idea that vascular endothelium influences not only the blood stream but also the smooth muscle cells, thus participating in the regulation of platelet aggregation and adhesion and of vascular tone. In 1988 EDRF was identified as nitric oxide (NO), a highly diffusible and short-lived free radical, synthesized by NO synthase from L-arginine (Palmer et al. 1988a). Specific inhibitors of NO synthase (NOS), introduced by Palmer et al. (1988b), enabled us to clarify the physiological roles of endogenous NO. This lipophilic gas molecule is now recognized to be a new intercellular messenger not only in the circulatory system but also in the central nervous and immune systems.

Responsiveness of Isolated Veins to Vasoactive Substances

Although attention is currently directed to responsiveness of capacitance vessel to chemical, neural, and physical stimuli as an important factor regulating the circulating blood volume and venous return, information available so far is limited. This chapter includes data on mechanical responses of isolated veins from dogs and monkeys to endogenous vasoactive substances, such as acetylcholine, histamine, angiotensin II, prostaglandin I2 and nitric oxide. It also compares responses of veins and arteries obtained from the same regions. As far as the blood vessels used are concerned, endogenous prostaglandin I2 appears to modulate venous functions more than those of arteries, whereas endothelium-derived relaxing factor may be a more preferential modulator in the arteries than in the veins.