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S Moncada

Publications and source records attributed to S Moncada.

At least 415 records · Page 23Linked to original sources
PubMed1980

Prostacyclin.

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Animals↗
PubMed1980

Interrelationships between prostacyclin and thromboxane A2.

Prostacyclin is a product of arachidonic acid metabolism generated by the vessel wall of all mammalian species studied including man. Prostacyclin is a potent vasodilator and the most potent inhibitor of platelet aggregation so far described. It inhibits platelet aggregation through stimulation of adenylate cyclase leading to an increase in cyclic AMP in the platelets. The enzyme which synthesizes prostacyclin is mainly localized in the endothelial layer of the vascular wall. Prostacyclin can also be a circulating hormone constantly released by the pulmonary circulation. On the basis of these observations we proposed that platelet aggregability in vivo is controlled via a prostacyclin mechanism. In contrast to the vessel wall, in blood platelets arachidonic acid is converted by the enzyme thromboxane synthetase to a potent vasoconstrictor and proaggregating substance, thromboxane A2. Therefore arachidonic acid is metabolized in the vessel wall and the platelets to potent substances with opposing biological activities. The balance between the activities of these substances is important in the homeostatic interaction of the platelets and the vessel wall. The different ways of interfering with this balance and its impact in the development of thrombosis and atherosclerosis are discussed. The balance between thromboxane A2 and prostacyclin might be important in the control of the pulmonary circulation. This possibility is discussed in the light of the present evidence.

Animals↗
PubMed1980

Prostacyclin release and the modulation of some vasoactive hormones.

Prostaglandin release into the circulation of the dog was studied by means of the blood-bathed bioassay system of Vane. Bradykinin, angiotensin II and angiotensin I selectively released a prostacyclin-like substance into the circulation, whereas no release was detected with adrenaline, noradrenaline, 5-hydroxytryptamine or acetylcholine. Release induced by bradykinin was mainly of renal origin, whereas that induced by the angiotensins was of more widespread origin, including the lungs and kidneys. No thromboxane A2 or prostaglandin-like substance could be detected from blood by any of these stimuli. Prostacyclin released by bradykinin contributed to the vascular actions of the kinin as indicated by treatment with cyclo-oxygenase inhibitors. Prostacyclin release also contributed to a reduced pressor effect of angiotensin II. This study indicates that prostacyclin release induced by the vasoactive peptides modulates some of their vascular actions.

Angiotensin I↗
PubMed1980

Effects of intravenous infusion of prostacyclin (PGI2) in man.

Prostacyclin infused intravenously in human volunteers induces ex vivo inhibition of platelet aggregation, tachycardia and hypotension. The inhibition of platelet aggregation is obtained with slightly lower doses than those which exhibit cardiovascular effects. The cardiovascular effects disappeared within a few minutes after discontinuing the infusion of prostacyclin but the platelet effects were longer lasting. Prostacyclin did not have any effect on platelet count, platelet factor 3, accelerated partial thromboplastin time, prothrombin time, euglobulin clot lysis time, fibrinogen degradation products, blood glucose concentration or urine sodium potassium ratio.

Adult↗
PubMed1980

Short term suppression of hyperacute renal allograft rejection in presensitised dogs with prostacyclin.

One of the main features of hyperacute renal allograft rejection in presensitised dogs is platelet aggregation within the kidney as detected by light microscopy and renal arterio-venous platelet counts. Graft failure, as determined by reduction and ultimate cessation of renal blood flow and urine production, can be abrogated in the short term by prostacyclin which is the most potent inhibitor of platelet aggregation yet discovered. After 4 h of extracorporeal perfusion, by which time all control kidneys had been rejected, all prostacyclin treated kidneys had normal or above normal blood flow rates, were producing urine and were similar histologically (light microscopy) to 4-hour autografts.

Animals↗
PubMed1980

Carbacyclin--a potent stable prostacyclin analogue for the inhibition of platelet aggregation.

Carbacyclin is a chemically stable analogue of prostacyclin. As an inhibitor of platelet aggregation induced by ADP or collagen in vitro, carbacyclin is 0.03 times as active as prostacyclin in human, dog or rabbit plasma. Carbacyclin, like prostacyclin, reduces systemic arterial blood pressure (BP) in dogs, rabbits and rats and is not inactivated during passage through the pulmonary circulation. Further actions were investigated using a new ex vivo technique which allows rapid preparation of platelet-rich plasma and determination of platelet aggregation. In the dog, intravenous infusion of carbacyclin or prostacyclin inhibits platelet aggregation ex vivo with minimal effects on BP or heart rate. In the anaesthetised or conscious rabbit, carbacyclin and prostacyclin produces similar cardiovascular changes in doses producing an equivalent degree of platelet inhibition. In both rabbit and dog, carbacyclin is 0.1 times as active as prostacyclin in inhibiting ex vivo platelet aggregation. Platelet inhibition is maintained throughout the period of infusion of either compound (up to 3 h) yet is no longer apparent 10 min after terminating the infusion. Carbacyclin is thus a chemically-stable but metabolically-unstable analogue with a biological profile closely similar to prostacyclin.

Adenosine Diphosphate↗
PubMed1980

Experimental assessment of prostacyclin in the harvesting of kidneys for transplantation.

Prostacyclin is a potent vasodilator and the most potent inhibitor of platelet aggregation yet discovered. A possible role for prostacyclin in the harvesting of kidneys in experimental canine transplantation has been investigated. Prostacyclin gives a 52.6% increase in renal blood flow prenephrectomy despite inducing a 23% drop in mean arterial blood pressure, without changing the rate of urine output. There is an associated drop in renal vascular resistance of 50.2% and an increase in renal blood volume of 25%. The value of heparin treatment before donor nephrectomy is confirmed as it improves the flow of flushing solution through the kidney after nephrectomy and improves red blood cell washout from the kidney. Prostacyclin and heparin together improve these parameters further. After a warm ischemic period of 45 min, autotransplanted kidneys in dogs pretreated with prostacyclin had normal renal function within 48 hr as judged by the serum creatinine whereas untreated dogs had permanent impairment of function.

Animals↗
PubMed1980

Prostacyclin eliminates the thrombocytopenia associated with charcoal hemoperfusion and minimizes heparin and fibrinogen consumption.

To evaluate the effects of prostacyclin (PGI2) on the bioincompatibility of charcoal hemoperfusion (CHP), platelet counts, platelet aggregate formation as measured by screen filtration pressure (SFP), plasma fibrinogen levels, and heparin activity monitored by calcium-thrombin clotting times (Ca-TCT) were compared during CHP in healthy dogs with heparin alone or heparin plus PGI2. Platelet losses (25 +/- 6 vs 83 +/- 2%: mean +/- SEM), rise in SFP (65 +/- 6 vs 249 +/- 25 mmHg), and fibrinogen consumption (20 +/- 5 vs 46 +/- 6%) were significantly less during CHP with PGI2 than with heparin only. In addition, rapid neutralization of heparin, as monitored by Ca-TCT, during CHP was prevented by PGI2. The use of PGI2 may allow a proper evaluation of the efficacy of CHP in conditions such as fulminant hepatic failure where, hitherto, incompatibility between blood and charcoal may have had deleterious effects.

Animals↗
PubMed1980

Prostacyclin and thromboxane A2 synthesis by rabbit pulmonary artery.

Superfused spiral strips of rabbit intrapulmonary artery (i.p.a.) were contracted by arachidonic acid (AA) and by the following substances in order of potency: prostaglandin (PG) endoperoxide analog (U46619) > PGH2 > PGF2 alpha. Intrapulmonary artery strips were consistently relaxed by PGE2 and by the enzyme inhibitors, indomethacin, aspirin, meclofenamic acid and 1-pentylimidazole. These latter inhibitors of cyclooxygenase and thromboxane (TX) synthetase also blocked the AA-induced contraction of rabbit i.p.a. Prostacyclin had no effect on the i.p.a. or produced either a small contraction or relaxation. TXA2, formed by incubating horse platelet microsomes with PHG2, always contracted the tissue and was more potent than the parent endoperoxide. Incubations of [14C]AA with i.p.a. produced mainly [14C]-6-keto-PGF1 alpha (he breakdonw product of prostacyclin ) and [14C]TXB2 (the breakdown product of TXA2); the identities of these products were confirmed by radioimmunoassay and by gas chromatography-mass spectrometry. The synthesis of TXB2 by i.p.a. cannot be attributed to adhering lung tissue or platelets and appears to be produced by the vascular tissue itself. It is concluded that, although both prostacyclin and thromboxane may contribute to the resting tone of the rabbit i.p.a., the response to AA is mainly due to production of TXA2.

Animals↗