Prostacyclin (PGI2) induces coronary vasodilatation in anaesthetised dogs

Dusting, Gregory J.; Chapple, D. J.; Hughes, R.; Moncada, Salvador; Vane, John R.

doi:10.1093/cvr/12.10.620

Cited by 68 publications

(32 citation statements)

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“…Release ofprostacyclin from the vascularcompartment into the epicardial irrigation fluid Prostacyclin, infused intravenously at 30, 100 and 300 ng kg-l min'l, decreased arterial pressure by up to 60 mmHg and increased heart rate up to 80 beats/min as observed previously (Dusting et al, 1978a). However, even at the highest infusion rate, prostacyclin could just be detected in the epicardial irrigation fluid by the bioassay tissues, in amounts equivalent to less than 1-2 nglml.…”

Section: Effects Ofpericardiectomysupporting

confidence: 73%

“…However, on the whole, the evidence is against prostaglandins making a major contribution to coronary autoregulation following changes in perfusion pressure, to hypoxic coronary vasodilatation, or to reactive hyperaemia (with the possible exception of the increases in blood flow following long periods of coronary occlusion) (Needleman & Kaley, 1978;Belloni, 1979). The concentrations of prostacyclin achieved in the epicardial fluid in the present experiments, high as they are, may not be sufficient to influence total coronary vascular resistance (Dusting et al, 1978a).…”

Section: Discussioncontrasting

confidence: 51%

“…It is likely that the visceral membrane of the pericardium, which is also lined with mesothelium, is a major source of this substance because the myocardium is a poor producer of prostanoids (Sivakcoff etal., 1979;our unpublished observations). Furthermore, very large concentrations of prostacyclin in the coronary vasculature, which had marked effects on coronary vascular resistance and arterial pressure (Dusting et aL, 1978a), were necessary to achieve release of 1-2 ng/ml into the epicardial irrigation fluid. Higher concentrations of endogenous prostacyclin were reached in the epicardial fluid with moderate elevations of cardiac work.…”

Section: Discussionmentioning

confidence: 99%

“…One concept of this mechanism is that a mediator or mediators generated locally in the myocardium acts as a dilator of arterioles, thereby increasing capillary blood flow. Prostacyclin is a potential candidate for this role since it is a potent coronary vasodilator (Dusting, Chapple, Hughes, Moncada & Vane, 1978a) and it is released from Langendorff-perfused hearts in vitro(De Deckere, Nugteren & Ten Hoor, 1977;Schror, Moncada, Ubatuba & Vane, 1978;Needleman, Bronson, Wyche, Sivakoff & Nicolaou, 1978).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, prostacyclin elicits a rapid increase in coronary blood flow when applied to the epicardial surface of the dog's heart (Dusting et al, 1978a). It therefore seemed possible that prostacyclin of pericardial origin might contribute to regulation of epicardial coronary blood flow.…”

Section: Introductionmentioning

confidence: 99%

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Stimulation of Prostacyclin Release From the Epicardium of Anaesthetized Dogs

Dusting

Nolan

1981

British J Pharmacology

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1 The generation of prostanoids in the hearts of anaesthetized dogs was studied by irrigating in situ the epicardial surface with Krebs solution. Prostanoids were measured by direct bioassay on smooth muscles and by radioimmunoassay of 6-oxo-prostaglandin Fl,. (6-oxo-PGF1,) and prostaglandin E2 (PGE2) in the epicardial irrigation fluid. 2 The epicardial irrigation fluid contained a prostacyclin-like substance, as indicated by the bioassay tissues, and immunoreactive 6-oxo-PGF1c; PGE2-like materials were also detected. By both methods the output of the prostacyclin-like substance, which decreased with time of epicardial irrigation, was increased by manipulating the heart and by adding arachidonic acid (3 pg/ml), and decreased by adding indomethacin (1 pg/ml) to the irrigating fluid.3 Bioassayed prostacyclin and immunoreactive 6-oxo-PGFi, in the epicardial irrigation fluid increased by about 3-5 ng/ml during and after infusion of isoprenaline (0.1 g kg-1 min-). The substance was not released by isoprenaline when indomethacin was added to the irrigating fluid, or when propranolol (0.5 mg/kg) was given intravenously. 4 Aortic constriction, bilateral carotid artery occlusion and intravenous angiotensin infusion all increased output of the prostacyclin-like substance into the epicardial irrigation fluid. The output was abolished by treating the heart with indomethacin (10 mg/kg intravenously or 1 jig/ml epicardially). 5 The prostacyclin-like substance was also released by all of the above stimuli after the parietal pericardium had been removed and replaced by a plastic sheet. 6 It is concluded that prostacyclin is continually released from tissues close to the epicardial surface and from the pericardium, and that prostacyclin generation increases when cardiac workload increases. Prostacyclin of epicardial or pericardial origin might therefore contribute to metabolic regulation of coronary blood flow.

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Section: Effects Ofpericardiectomysupporting

confidence: 73%