Endothelium‐dependent Vasodilatation in Bovine Coronary Arteries: Calcium Dependence and Inhibition by Proadifen

Macdonald, Peter S.; Dubbin, Philip N.; Dusting, GJ

doi:10.1111/j.1440-1681.1986.tb00359.x

Cited by 5 publications

(4 citation statements)

References 14 publications

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“…The rings were bathed in Krebsbicarbonate solution, maintained at 37°C and gassed with 5% CO, in oxygen. In some rings, the endothelium was removed by gently rubbing the intimal surface with a fine wooden taper, as in our previous studies (Macdonald et al 1986). The rings were allowed to equilibrate for 45 min during which time resting passive tension was adjusted to 4 g. Tension was measured isometrically with Grass FT03C strain gauge transducers coupled to Rikadenki recorders.…”

Section: Isolated Coronary Artery Preparationsmentioning

confidence: 99%

“…These authors proposed that a-agonists stimulate release of an endothelium-derived relaxing factor (EDRF) through an a,-receptor located on the endothelial cells. The chemical nature of EDRF is unknown, although there is some evidence that its release could involve mobilization and release of arachidonic acid from membrane phospholipids (Furchgott 1983;Singer & Peach 1983;Macdonald et al 1986).…”

Section: Introductionmentioning

confidence: 99%

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Β‐adrenoceptors on Endothelial Cells Do Not Influence Release of Relaxing Factor in Dog Coronary Arteries

Macdonald

Dubbin

Dusting

1987

Clin Exp Pharma Physio

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1. The aim of this study was to determine if stimulation of a beta-adrenoceptor on endothelial cells could release an endothelium-derived relaxing factor (EDRF) similar to that released by acetylcholine. 2. In dog coronary rings preconstricted with PGF2 alpha or serotonin, removal of the endothelium did not alter the relaxant responses to isoprenaline. However, in rings preconstricted with the thromboxane-mimetic U46619, removal of the endothelium enhanced the response to isoprenaline. 3. The vasorelaxant responses to isoprenaline in endothelium-denuded rings were inhibited in a concentration-dependent manner by the specific beta 1-adrenoceptor antagonist CGP-20712A (3-100 nmol/l), but were not altered by the beta 2-adrenoceptor antagonist ICI-118551 (30 nmol/l). 4. The vasorelaxant responses to isoprenaline in the presence of CGP-20712A (30 nmol/l) or ICI-118551 (30 nmol/l) were not impaired by removal of the endothelium. 5. Endothelium-dependent vasorelaxant responses to acetylcholine and bradykinin were not altered by isoprenaline (0.1 mumol/l) in the presence of CGP-20712A (30 nmol/l). 6. Therefore, the beta-adrenoceptors on dog coronary artery smooth muscle which produce relaxation are predominantly of the beta 1-subtype. Stimulation of any beta 2-adrenoceptors on the endothelium in dog coronary artery does not release EDRF, and does not modulate endothelium-dependent vasodilatation induced by other agents.

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Section: Isolated Coronary Artery Preparationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Β‐adrenoceptors on Endothelial Cells Do Not Influence Release of Relaxing Factor in Dog Coronary Arteries

Macdonald

Dubbin

Dusting

1987

Clin Exp Pharma Physio

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“…A number of compounds, broadly described as anti-oxidants, have been shown to block endothelium-dependent dilatation of isolated blood vessels (Furchgott 1984). Some of these compounds inhibit enzymes of arachidonic acid oxygenation, or reduce carbonyl groups, and for these reasons EDRF was variously postulated to be a lipoxygenase product of arachidonic acid (Furchgott 1983;Forsterman & Neufang 1985), a product of cytochrome P450 mono-oxygenase (Singer et al 1984;Pinto et al 1985;Macdonald et al 1986), or a ketone, aldehyde or lactone (Griffith et al 1984). However, from these experiments it is not clear whether the compounds are acting at the level of the endothelium or on the smooth muscle effector; they could also act to accelerate inactivation of the factor or block its conversion to an active mediator in the smooth muscle.…”

Section: Introductionmentioning

confidence: 99%

The Inhibitory Actions of Anti‐oxidants on Endothelium‐derived Relaxing Factor Released From Cultured Bovine Cells

Read¹,

Dusting²

1987

Clin Exp Pharma Physio

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“…Some of these were sufficiently successful for a half‐life for EDRF to be calculated (Griffith et al , 1984; Cocks et al , 1985; Forstermann et al , 1985). Many other experiments were carried out attempting to identify the chemical structure of EDRF and to inhibit its activity (Singler et al , 1984; Pinto et al , 1985; MacDonald et al , 1986).…”

mentioning

confidence: 99%

Bioassay of prostacyclin and endothelium‐derived relaxing factor (EDRF) from porcine aortic endothelial cells

Gryglewski¹,

Moncada²,

Palmer³

1997

British J Pharmacology

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This paper represented the interface between two long and very productive periods of research. The first of these started in 1976 with our discovery of thromboxane synthase (Needleman eta]., 1976) and prostacyclin (Moncada et a1 1976a) and the second began with this paper and led to the discovery the following year of the identity of EDRF as nitric oxide (NO) (Palmer et ul., 1987) and the subsequent elucidation of its many biological roles.Endothelium-dependent relaxation and EDRF had been identified by Furchgott and Zawadzki (1980) using fresh vascular tissues and many people had confirmed their findings using a variety of tissues (see Furchgott, 1984; Moncada et al., 1987); Vanhouttc, 1989). A number of experiments were carried out attempting to transfer biologically active EDRF from one piece of vascular tissue to another. Some of these were sufficiently successful for a half-life for EDRF to be calculated (Griffith el ul., 1984; Cocks et al., 1985; Forstermann et al., 1985). Many other experiments were carried out attempting to identify the chemical structure of EDRF and to inhibit its activity (Singler et al., 1984; Pinto et al., 1985; MacDonald et al., 1986).We tried to approach the problem in a different way. The difficulties associated with the research on EDRF at that time were related to the indirect nature of the majority of the experiments in which endothelium-dependent relaxation was measured or, when working with endothelium-derived relaxing factor, to the very small amounts of material that were being used. We thought that if proper pharmacological studies were to be carried out and the chemical structure was to he identified then we needed a larger quantity of material and a reliable and, as much as possible, a quantitative bioassay system. We decided to culture endothelial cells on microcarrier beads and to perfuse them in a modified chromatography column. We used the perfusate to superfuse a series of bioassay tissues, both vascular and non-vascular, which when combined appropriately allowed the differential bioassay of prostacyclin and EDRF.The system was useful in several ways since, first, it allowed the culture of many millions of endothelial cells which opened the door to further important studies. Secondly, although the cells were not as responsive as vascular tissue, they did respond to substances such as bradykinin and the Ca2+ ionophore A23 187 by releasing both prostacyclin and EDRF and this allowed the study of some of the biological characteristics of EDRF itself. Thirdly, the bioassay superfusion technique, as many times before (see Vane, 1964), proved to be immensely informative and reliable.We were particularly well placed to do this work since, during the mid-l970s, we had gained a great deal of experience doing bioassay of unstable arachidonic acid metabolites such as prostacyclin and thromboxane A, (TXA,), which had a half life of approximately 30 s. With Stuart Bunting we had struggled and succeeded in bioassaying TXA, generated from different sources (Moncada et al., I...

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Endothelium‐dependent Vasodilatation in Bovine Coronary Arteries: Calcium Dependence and Inhibition by Proadifen

Cited by 5 publications

References 14 publications

Β‐adrenoceptors on Endothelial Cells Do Not Influence Release of Relaxing Factor in Dog Coronary Arteries

Β‐adrenoceptors on Endothelial Cells Do Not Influence Release of Relaxing Factor in Dog Coronary Arteries

The Inhibitory Actions of Anti‐oxidants on Endothelium‐derived Relaxing Factor Released From Cultured Bovine Cells

Bioassay of prostacyclin and endothelium‐derived relaxing factor (EDRF) from porcine aortic endothelial cells

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