The nature of endothelium-derived vascular relaxant factor

Abstract

The existence of endothelium-derived vascular relaxant factor (EDRF) was postulated by Furchgott and colleagues when they observed that acetylcholine paradoxically relaxed preconstricted aortic strip preparations by an endothelium-dependent mechanism. This phenomenon has since been demonstrated in different blood vessels and mammalian species and it can be elicited by several other agents. EDRF has been thought to be a humoral agent, a lipoxygenase derivative and possibly a free radical. In the study reported here, by using aortic preparations from the rabbit, alone and in cascade experiments with isolated perfused coronary preparations, we demonstrate definitively that EDRF is a humoral agent. It is released from unstimulated aortic preparations containing endothelium, its release can be stimulated for prolonged periods by acetylcholine, and it is not a lipoxygenase derivative or free radical but an unstable compound with a carbonyl group at or near its active site.

Differentiation by hydroquinone of relaxations induced by exogenous and endogenous nitrates in non‐vascular smooth muscle: role of superoxide anions

“…It is unlikely that lack of penetration of hydroquinone into the tissue can account for its differentiation between exogenous and endogenous nitrate in the present study because it produced the expected reversal of EDRF/ NO-induced relaxations of rabbit aorta (Furchgott, 1984 (Colter & Quastel, 1950;Mittal et al, 1978;Martin et al, 1985;Laurence & Bennett, 1987 (Graser et al, 1990;Myers et al, 1990;Rubanyi et al, 1990), and it may be that a similar substance is liberated from the NANC nerves. Several physiologically-relevant Snitrosothiols have recently been shown to relax smooth muscle (Kowaluk & Fung, 1990) (Griffith et al, 1984) or as a generator of superoxide anions (Moncada et al, 1986). Our observations with SOD and with the chemiluminescent assay suggest that superoxide anion generation cannot explain the inhibitory effect of hydroquinone on NO in the present study.…”

“…endogenous nitrate NANC system; indeed, such evidence would be necessary to establish NO as a neurotransmitter. Hydroquinone has been used frequently as an inhibitor of EDRF/NO relaxations of vascular smooth muscle (Furchgott, 1984) where it might act either as a free radical scavenger (Griffith et al, 1984) or as a generator of superoxide anions (Moncada et al, 1986). However, its effects on NANC responses have been less widely studied and results have been varied; Gillespie & Sheng (1990) found that hydroquinone produced a small reduction of NANC relaxations of the rat anococcygeus but had no effect on the bovine retractor penis.…”

A comparison of haemoglobin and erythrocytes as inhibitors of smooth muscle relaxation by the NANC transmitter in the BRP and rat anococcygeus and by EDRF in the rabbit aortic strip

“…It has, however, several properties in common with EDRF. For example, both relax the BRP (Gillespie & Sheng, 1988a,b), both increase cyclic GMP (Rapoport & Murad, 1983;Diamond & Chu, 1983;Bowman & Drummond, 1984), both are abolished by anoxia (Furchgott & Zawadzki, 1980;Bowman & McGrath, 1985) and by borohydride (Griffith et al, 1984;Gillespie & Sheng, unpublished observation), as well as by haemoglobin. If EDRF is nitric oxide, it is possible that the NANC transmitter is also nitric oxide.…”

EDRF‐mediated dilatation in the rat isolated perfused kidney: a microangiographic study

“…The endothelium-dependent relaxation of arterial Zawadski, 1980;Griffith et al, 1984), identical with smooth muscle which can be induced by a wide or closely related to nitric oxide (Ignarro et al, 1987; variety of compounds such as acetylcholine (ACh), is Palmer et al, 1987;Furchgott, 1988), and is avidly mediated by stimulated release of endotheliumbound by haemoglobin (Kelm et al, 1988). derived relaxing factor (EDRF).…”