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Biomedical subjects

S Moncada

Publications and source records attributed to S Moncada.

At least 397 records · Page 22Linked to original sources
PubMed1982

6-oxo-prostaglandin F1 alpha and thromboxane B2 in uterine vein blood--a possible role in menstrual bleeding.

The role of the haemostatic system in relation to menstrual bleeding is poorly understood. Platelet retention to glass beads and plasma concentrations of 6-oxo-PGF1 alpha and thromboxane B2 were measured in uterine and peripheral venous blood obtained from 18 women undergoing abdominal hysterectomy. Concentrations of 6-oxo-PGF1 alpha were significantly (p less than 0.01) higher in uterine (1.4 +/- 0.3 ng/ml, mean +/- SEM) than in peripheral vein blood (0.2 +/- 0.1 ng/ml) as was the level of thromboxane B2 (0.5 +/- 0.1 and 0.2 +/- 0.1 ng/ml, respectively). Platelet retention in uterine vein blood (11 +/- 4%) was significantly lower than in peripheral blood (42 +/- 4%; p less than 0.01) and the degree of platelet retention correlated inversely with the plasma concentration of 6-oxo-PGF1 alpha (r -0.43; p less than 0.01). There was a significant rank correlation between time since menstruation and concentrations of 6-oxo-PGF1 alpha in uterine (tau + 0.69; p less than 0.001) and peripheral (tau + 0.56; p less than 0.05) vein blood. The results indicate that an increased local production of prostacyclin (PGI2) relative to thromboxane A2 at the time of menstruation could contribute to the mechanism of uterine bleeding.

Adult↗
PubMed1982

Effects of isolation and culture on prostaglandin synthesis by porcine aortic endothelial and smooth muscle cells.

Freshly isolated neonatal porcine aortic tissue (smooth muscle with or without endothelium present) produced approximately 30 ng/mg wet tissue of 6-oxo-prostaglandin F1 alpha (the stable hydrolysis product from prostacyclin) and approximately 15 ng/mg of prostaglandin E2, as measured by radioimmunoassay after 24 h incubation in culture medium. Primary cultures of porcine endothelial and smooth muscle cells (isolated by enzymic digestion of aortic tissue) exhibited the same pattern of prostaglandin production, but absolute values were greater than for fresh tissue, particularly in the case of endothelium. Subcultures of endothelium produced smaller amounts of prostaglandins, although the pattern remained similar. In contrast, subcultures of smooth muscle cells produced a greater total amount of prostaglandins than did primary cultures, and the main product was prostaglandin E2. Experiments with [14C] prostaglandin H2 or [14C]arachidonic acid confirmed that aortic tissue, cultured endothelium, and primary cultures or aortic smooth muscle cells synthesized prostacyclin, and demonstrated that subcultured smooth muscle cells enzymically isomerised prostaglandin H2 to prostaglandin E2. Kinetic studies showed that prostaglandin production by cultured vascular cells was transiently increased by subculture or changing the growth medium, and that production per cell declined with increasing cell density. The change in pattern of prostaglandin production during culture was shown to be due to a rapid decline in the rate of prostacyclin production (which apparently began immediately after tissue isolation), together with a more gradual rise in prostaglandin E2 production. These results indicate that the amounts and ratios of prostaglandins produced by vascular endothelial and smooth muscle cells are greatly affected by the conditions used to isolate and culture the cells; vascular cells in vivo may similarly alter their pattern of prostaglandin production in response to local changes in their environment.

Animals↗
PubMed1982

A comparison of the inhibitory effects of prostacyclin and carbacyclin on platelet adhesion to collagen.

The effect of carbacyclin, a chemically stable analogue of prostacyclin (PGI2), on the adhesion of platelets to collagen has been examined. The compound was compared to PGI2 which is unstable and rapidly hydrolysed to the inactive derivative, 6-oxo-PGF 1 alpha. The adhesion of 111Indium-labelled human platelets to collagen in the absence of platelet aggregation and secretion was measured. The cAMP level in the platelets was also monitored. Both PGI2 and carbacyclin inhibited platelet-collagen adhesion and caused a rise in the platelet cAMP level. Carbacyclin was approximately 15-fold less effective than PGI2, however, its effect was longer lasting, remaining constant for at least 30 minutes.

Blood Platelets↗
PubMed1982

The use of prostacyclin in the separation from plasma and washing of human platelets.

A new method for the separation from plasma and washing of human platelets is described. The use of prostacyclin (PGI2) throughout the procedure prevents the activation of platelets. The method allows a 60-70% yield of platelets from PRP. The platelet sensitivity to ADP, collagen, adrenaline, arachidonic acid and thrombin is the same as in PRP. The platelet suspension is stable for long periods and the reactivity to aggregating agents remains unchanged for periods greater than 48 h when platelets are stored at 4 degrees C.

Adenosine Diphosphate↗
PubMed1982

The salvage of ischaemic myocardium by BW755C in anaesthetised dogs.

BW755C, a dual inhibitor of the lipoxygenase and cyclo-oxygenase pathways of arachidonic acid metabolism reduces the size of an infarct produced by 60 min of coronary occlusion followed by 5 hours reperfusion in anaesthetised beagles. This effect of BW755C is observed when the drug is given after the period of occlusion, and is independent of any haemodynamic effect. In contrast, indomethacin, which inhibits only the cyclo-oxygenase pathway, did not influence infarct size. It is suggested that the salvage of acutely ischaemic myocardium by BW755C is due to inhibition of lipoxygenase product formation by migrating cells which invade the damaged myocardium to produce an inflammatory response.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1982

Prostacyclin can either increase or decrease heart rate depending on the basal state.

1 The influence of the basal heart rate on the change in rate induced by prostacyclin (PGI2) was investigated in beagles anaesthetized with chloralose. 2 In male dogs with a low basal heart rate (less than 100 beats/min) PGI2, in doses up to 0.5 microgram/kg intravenously, induced hypotension and tachycardia. 3 In contrast, PGI2-induced hypotension was accompanied by bradycardia when either the basal heart rate was increased (greater than 130 beats/min) with isoprenaline or nitroprusside, or the dose of PGI2 was increased. 4 Female beagles were less sensitive than males to the stimulation of a reflex bradycardia by PGI2. 5 The influence of prostaglandin E2 (PGE2) and bradykinin on heart rate was also found to depend upon the basal state in some dogs. 6 Bilateral vagotomy reversed the bradycardia provoked by PGI2, PGE2 and bradykinin. 7 Thus, PGI2-induced bradycardia in dependent on both the dose and the basal heart rate. Similarly the effects of PGE2 and bradykinin on heart rate also depend upon the basal state in some dogs. Moreover, there is a correlation between the ability of all three agonists to induce bradycardia, suggesting a common mechanism of action.

Animals↗
PubMed1981

Prostacyclin: its biosynthesis, actions and clinical potential.

Prostacyclin (PGI2) is the 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. Prostacyclin inhibits aggregation through stimulation of platelet adenyl cyclase leading to an increase in platelet cyclic AMP. In the vessel wall, the enzyme that synthesizes prostacyclin is concentrated in the endothelial layer. Prostacyclin can also be a circulating hormone released from the pulmonary circulation. Based on these observations we proposed that platelet aggregability in vivo is controlled via a prostacyclin mechanism. The discovery of prostacyclin has given a new insight into arachidonic acid metabolism and has led to a new hypothesis about mechanisms of haemostasis. Reductions in prostacyclin production in several diseases, including atherosclerosis and diabetes, have been described and implicated in the pathophysiology of these diseases. Additionally, since prostacyclin powerfully inhibits platelet aggregation and promotes their disaggregation, this agent could have an important use in the therapy of conditions in which increased platelet aggregation takes place and in which, perhaps, a prostacyclin deficiency exists. Prostacyclin has been used beneficially in humans during extracorporeal circulation procedures such as cardiopulmonary bypass, charcoal haemoperfusion and haemodialysis. Its possible use in other conditions such as peripheral vascular disease or transplant surgery is at present being investigated.

Angiotensin I↗
PubMed1981

Prostacyclin and blood coagulation.

Prostacyclin is a potent but unstable vasodilator, and inhibitor of platelet aggregation, which is produced by blood vessel walls. Platelet aggregability may be constantly conditioned in vivo by local or circulating prostacyclin. Prostacyclin is important in the maintenance of vascular homeostasis and may be implicated in certain disease states. The use of prostacyclin in antithrombotic therapy appears logical, considering its action in increasing platelet cyclic AMP and reducing aggregation; its potential in antithrombotic therapy is presently being explored.

Arteriosclerosis↗
PubMed1980

Prostacyclin mediates the potentiated hypotensive effect of bradykinin following captopril treatment.

The effect of angiotensin-converting enzyme inhibition by captopril on the release of a prostacyclin-like substance by bradykinin, angiotensin I and angiotensin II was studied by means of the blood-bathed bioassay technique of Vane. Administration of captopril abolished the release of prostacyclin-like substance induced by angiotensin I, potentiated the release provoked by bradykinin and did not alter that due to angiotensin II. Potentiation of the bradykinin-induced renal vasodilatation with captopril could be completely reversed by indomethacin, which also abolished the kinin-induced release of prostacyclin-like substance. Potentiation of the bradykinin-induced hypotension was markedly attenuated but not completely reversed by cyclo-oxygenase inhibition. It is suggested that following converting inhibition increased production of prostacyclin by elevated kinin levels may contribute to the antihypertensive action of angiotensin-converting enzyme inhibitors.

Angiotensin I↗
PubMed1980

The effects of non-steroid anti-inflammatory drugs on leukocyte migration in carrageenin-induced inflammation.

Some non-steroid anti-inflammatory drugs which inhibit arachidonate cyclo-oxygenease have been examined for their effects on leukocyte migration, prostaglandin production and oedema formation in carrageenin-induced inflammation in the rat. At doses which inhibited oedema, all the drugs tested caused a dose-dependent reduction in numbers of leukocytes and prostaglandin concentrations in 24-h inflammatory exudates. At lower doses, indomethacin, aspirin, sodium salicylate, flurbiprofen and phenylbutazone significantly potentiated leukocyte migration by 20-70%. Ibuprofen, naproxen and BW755C reversed the indomethacin-induced increase in leukocyte accumulation. BW755C inhibits the generation of chemotactic lipoxygenase products and it is possible that the effects of all these drugs on leukocyte migration are mediated through the lipoxygenase pathway of arachidonic acid metabolism.

Animals↗