Endothelium — Influenced Vasomotion: Models and Measurements
Part of the
NATO ASI Series
book series (volume 166)
The chance discovery by Furchgott and colleagues in 1980 that acetylcholine relaxes isolated arterial strips only if their endothelium is carefully preserved has now clarified the mechanism of action of a wide variety of pharmacological agents and the physiology of flow regulation. “Sandwich” experiments in which an endothelium-intact aortic strip relaxed a closely apposed endothelium-denuded strip, suggested that the phenomenon was mediated by a diffusible vasodilator (Furchgott and Zawadzki, 1980; Furchgott, 1983) and this was confirmed by bioassay experiments (Griffith et al., 1984). This short review will focus on the properties and physiological significance of this agent, endothelium derived relaxing factor (EDRF). Endothelium-dependent relaxation is associated with hyperpolarization of underlying smooth muscle (Bolton et al., 1984) but recent evidence suggests that this is mediated by a separate factor (Komori and Suzuki, 1987; Feletou and Vanhoutte, 1988). Endothelium also produces an endothelium-derived contracting factor or EDCF, (Hickey et al., 1985; Gillespie et al., 1986) and a peptide, endothelin, which is one of the most potent vasoconstrictor agents yet discovered has now been sequenced and cloned (Yanagisawa et al., 1988). In addition to modulating the action of pharmacological agents, EDRF and EDCF, by responding to mechanical forces, may together account for the complementary homeostatic phenomena of flow-dependent dilatation and the so-called “myogenic” response. The former, an endothelium-dependent mechanism whereby the arterial lumen adjusts dynamically to alterations in flow rate (Schretzenmayr, 1933; Gerova et al, 1981; Holtz et al, 1983; Pohl et al, 1986a) seems to be mediated by EDRF release stimulated by shear stress. The “myogenic” response (Bayliss, 1902) is the mechanism whereby quick stretch or a rise in transmural pressure induces vasoconstriction, limits flow and thus contributes to autoregulation. There is evidence that this also depends on an intact endothelium in some (Harder, 1987; Katusic et al., 1987), although not all (Hwa and Bevan, 1986), artery types so that it is not always strictly “myogenic”. The specific involvement of endothelin, whilst likely, remains to be confirmed.
KeywordsDiameter Ratio Soluble Guanylate Cyclase Geometrical Similarity Endothelium Derive Relaxing Factor Individual Junction
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