Progress on the characterization and identification of endothelium‐derived relaxing factor(s)

Berkowitz, Barry A.; Ohlstein, Eliot H.

doi:10.1002/ddr.430070402

Cited by 5 publications

(4 citation statements)

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“…Endothelial-derived relaxing factor (EDRF), first described by Furchgott and colleagues [Furchgott, 1981Furchgott and Zawadski, 1980;Furchgott et al, 1981,19841, appears to be one of the most potent, important vasodilator substances released by the endothelium in response to circulating and neurogenically released humoral substances, such as platelets, serotonin (5-HT), histamine, thrombin, arachidonic acid, bradykinin, catecholamines, substance P, adenosinetriphosphate (ATP), and calcitonin-gene-related peptide. EDRF has been demonstrated in arteries from every species tested, including humans [for references see Berkowitz and Ohlstein, 1986;Busse et al, 1985;Greenberg et al, 1986a,b;Vanhoutte, ,1987Vanhoutte and Houston, 19851. EDRF was initially thought to be a hydroperoxide or free radical, derived from fatty acids, which stimulated guanylate cyclase (GC) within the VSM.…”

Section: Background History Of Edrfmentioning

confidence: 99%

“…The original concept that EDRF was a lipoxygenase-derived, labile hydroperoxide or free radical, derived from fatty acid metabolism, conferred regulatory mechanisms to the EDRF system that are sinlilar to those described for the prostaglandin-prostacyclin system: i.e., release of EDRF reflected de novo synthesis [Berkowitz and Ohlstein, 1986;Greenberg et al, 1986a,b;Vanhoutte, , 1987Griffith, 1985;Griffith et al, 1984Griffith et al, , 1986Vanhoutte and Houston, 1985). With the application of the bioassay system to EDRF studies [Gnffith et al, 1984;Rubanyi and Vanhoutte, 19851 and separation of the release of EDRF from its action on smooth muscle, the lipid and free radical nature of EDRF was challenged.…”

Section: Background History Of Edrfmentioning

confidence: 99%

“…Using a series of inhibitors of peptide synthesis and degradation, he demonstrated a peptide like nature for EDRF released by thrombin. Gryglewski et al [1986a,b] and Berkowitz and Ohlstein [1986], employing bovine, cultured endothelium cells coupled to microcarrier beads, and bioassay of effluent from the perfused endothelium cells, demonstrated that: 1) arachidonic acid. A-23 187, and bradykinin elicit release of EDRF, and 2) mecholyl did not elicit release of EDRF.…”

Section: Does a Family Of Edrf's Exist In Endothelium From Arteries?mentioning

confidence: 99%

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Endothelium‐derived relaxing and contracting factors: New concepts and new findings

Greenberg

Diecke

1988

Drug Development Research

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Greenberg, S. and F.P.J. Diecke: Endothelium-derived relaxing and contracting factors: New concepts and new findings. Drug Dev. Res. 12:131-149, 1988. The vascular endothelium is a source of both relaxing and contracting factors. These yet to be identified substances have been termed endothelium-derived relaxing factor(s) (EDRF) and endothelium-derived contracting factor($ (EDCF). The family of EDRF(s) appear to be important mediators of vascular relaxation and platelet disaggregation. Destruction of the endothelium or modulation of its structure, as occurs with coronary artery disease and atherosclerosis, results in impaired coronary and systemic arterial relaxation, vasospasm, and enhanced platelet aggregability. Acute and chronic hypertension blunts EDRF-induced vascular relaxation. Thus, EDRF appears to represent an endogenous modulator system of vascular smooth muscle-endothelium-platelet interaction in humans. Recent evidence supports the possibility that one EDRF may be nitric oxide, whereas a second EDRF may stimulate sodium-potassium ATP'ase. EDCF may be a family of at least three substances.One substance appears to be a low molecular weight polypeptide, is produced by hypoxia, and promotes a long-acting vasoconstriction associated with increased calcium influx into vascular smooth muscle. The second EDRF is of unknown origin, is diffusable, released by anoxia and hypoxia, and may facilitate the action of the leukotrienes and lipoxygenase products on vascular smooth muscle. The remaining EDCF may be derived from the actions of lipoxygenases on arachidonic acid and appears to be released by vasoconstrictor agonists, stretch and potassium ion. Further research is required to elucidate the functional role and nature of EDCF(s) on vascular smooth muscle.

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Section: Background History Of Edrfmentioning

confidence: 99%

Section: Background History Of Edrfmentioning

confidence: 99%

Section: Does a Family Of Edrf's Exist In Endothelium From Arteries?mentioning

confidence: 99%

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Endothelium‐derived relaxing and contracting factors: New concepts and new findings

Greenberg

Diecke

1988

Drug Development Research

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“…Peach et al (1985) have speculated upon the involvement of cytochrome P450-oxygenase in the synthesis of EDRF, based upon the inhibitory actions of SK&F 525A. As discussed by Berkowitz & Ohlstein (1986), despite the almost complete inhibition of endothelium-dependent relaxation responses given by this drug, its actions may well be mediated by its calcium channel blocking activity (Lee & Berkowitz, 1976;Long & Stone, 1985).…”

Section: Introductionmentioning

confidence: 99%

The inhibition of release of endothelium‐derived relaxant factor by manoalide, a potent inhibitor of phospholipase A₂

Long¹,

Sarau²,

Berkowitz³

1987

British J Pharmacology

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1 The inhibitory action of manoalide on vascular relaxation was characterized. Manoalide was a potent inhibitor ofendothelium-dependent relaxations in the isolated aorta of the rabbit. Responses to acetylcholine (ACh), A23 187 and substance P were reduced by manoalide in a dose-dependent manner whilst those to nitroglycerin were unaffected. 2 Repeated washing of manoalide-treated tissues did not restore the relaxant response to ACh, indicating an irreversible action of manoalide. Scanning electron microscopic studies revealed that the endothelium remained intact on manoalide-treated tissues. 3 Rabbit aortae from which the endothelium had been removed relaxed in response to perfusion with ACh when delivered via an upstream endothelium-bearing tissue, indicating release of an endotheliumderived relaxant factor (EDRF). Incubation of the tissue without endothelium with manoalide (100 nM; 30 min) or inclusion of manoalide in the superfusate at a point just distal to the endothelium bearing tissue did not reduce the relaxant potency of EDRF. 4 Contractile responses of the guinea-pig isolated ileum to ACh were not affected by manoalide and, furthermore, binding of [3H]-quinuclidinyl benzilate to striatal membranes was not reduced by manoalide except at very high concentrations. 5 Manoalide therefore appears to inhibit vascular relaxation with a selectivity directed towards that mediated by EDRF. A direct antagonism of neither cholinoceptors nor EDRF receptors occurs and it is suggested that manoalide acts at a site within the endothelium to inhibit the synthesis and/or release of EDRF. Based upon these and previous data the possibility that EDRF is lipid-like or controlled by an arachidonic acid metabolite must continue to be considered.

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Vasodepression ex vivo after administration of inflammatory mediatorsin vivo in the rat

Bekemeier

Sänze

1989

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When rats were pretreated by intraplantar or i.v. injection of various inflammatory mediators, the vasopressor effect of i.a. norepinephrine in the subsequently isolated perfused hindlegs of the rats was found to be partly depressed. This vasodepression could also be detected if mediators were directly co-perfused in the isolated hindlegs. The vasodepressor effect was strongest following histamine pretreatment and co-perfusion, respectively, whereas endotoxin 0111:B4, PAF-acether, PGE1, and LTD4 were less effective. Only weak or no vasodepression could be induced by bradykinin, serotonin, lysolecithin, and substance P (1-11). The significance of the results is discussed with respect to anaphylactic disorders.

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Progress on the characterization and identification of endothelium‐derived relaxing factor(s)

Cited by 5 publications

References 19 publications

Endothelium‐derived relaxing and contracting factors: New concepts and new findings

Endothelium‐derived relaxing and contracting factors: New concepts and new findings

The inhibition of release of endothelium‐derived relaxant factor by manoalide, a potent inhibitor of phospholipase A₂

Vasodepression ex vivo after administration of inflammatory mediatorsin vivo in the rat

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Progress on the characterization and identification of endothelium‐derived relaxing factor(s)

Cited by 5 publications

References 19 publications

Endothelium‐derived relaxing and contracting factors: New concepts and new findings

Endothelium‐derived relaxing and contracting factors: New concepts and new findings

The inhibition of release of endothelium‐derived relaxant factor by manoalide, a potent inhibitor of phospholipase A2

Vasodepression ex vivo after administration of inflammatory mediatorsin vivo in the rat

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The inhibition of release of endothelium‐derived relaxant factor by manoalide, a potent inhibitor of phospholipase A₂