Prostaglandins and medicine最新文献

We studied the effect of prostacyclin infusion on the soft tissue microcirculation. We used lymph flow Q_L and the lymph/plasma L/P protein ratio to reflect transvascular fluid flux and changes in microvescular hydrostatic pressure, Pmv.

Unanesthetized sheep with prefemoral lymph fistulae were infused with PGI₂ (0.2 ug/kg/min) for two hours. Changes in Q_L and L/P were compared to animals in which P_mv was increased by volume loading. During PGI₂, Q_L was significantly increased, as was cardiac output while mean aortic pressure decreased. The UP ratio did not decrease to the degree seen with a comparable increase in Q_L, due to an increase in P_mv. The increase in Q_L was most likely due to an increase in microvescular surface area. Q_L remained significantly increased for several hours after infusion and L/P decreased to the same degree as seen with an increase in P_mv. This indicates that Pmv is increased for several hours in soft tissue after PGI₂ infusion, due to a relative increase in venous resistance probably secondary to activation of the renin-angiotensin system.

We studied the effects of paraquat (25 mg/kg, free base, I.V.) on the circulating plasma levels of arachidonic acid, PGF2a and PGE2 in the beagle. The arachidonic acid level was quantified by GLC and prostaglandins by radioim unoassay.The plasma levels of arachidonic acid after paraquat treatment were decreased to 50.8% of control at 0.5 hrs. Thereafter the levels increased with time reaching a maximum level of 127.8% at 12 hrs, from which it decreased to 82.8% of control at 24 hrs. Concurrent with these changes in arachidonic acid, the plasma PGE₂ levels at 0.5, 1.5, 6.0, 12.0 and 24.0 hrs were significantly decreased to 65.4%, 42.5%, 52.4%, 41.0% and 50.3% of control levels, respectively. In contrast to these findings the plasma levels of PGF2a after paraquat treatment were insignificantly elevated at 0.5, 3.0, 6.0, 12.0, and 24.0 hrs, to 174.3%, 170.4%, 119.3%, 183.3% and 180.3% of control respectively. The ratio of PGE₂/PGF_2α exhibited a significant decrease at 12.0 and 24.0 hrs. Histopathological studies revealed insignificant changes of the lungs, but marked changes of the kidney. We concluded from these studies that changes in plasma levels of prostaglandins may be related to the acute nephrotoxicity caused by paraquat in dogs.

The epoxymethano analogs of PGH₂ caused rapid and persistent increase in perfusion pressure in isolated rat pancreata without significant effect on glucagon and insulin secretory responses to PGH₂ and PGE₂. The changes in perfusion pressure are interpreted as alterations in vascular resistance since the flow rate was kept constant at 2.5 mL per min. PGH₂ alone caused significant elevation in pressure. However, PGH2 administration superimposed upon an infused epoxymethano analog of PGH₂, decreased perfusion pressure significantly, whereas PGH₂ induced hormone release was not decreased. The analogs neither stimulated nor inhibited the endocrine pancreas secretion. These studies provide evidence for complete dissociation of vascular constriction from pancreatic hormone release and further suggest that the effects of PGH₂ on islet hormone secretion may result from the conversion of PGH₂ to other prostanoids.

This was an echocardiographic study of the cardiovascular effects of rostacclin (PGI₂) infused intravenously to human volunteers at the rate of 20 ng⊎ Kg⁻ ⊎ min⁻ for 10 Anutes. The following parameters were recorded in the steady state , at one-minute intervals throughout infusion and the ensuing recovery period: systolic, diastolic, and mean blood pressure ( SBP, DBP, MBP); heart rate (HR); left ventricle end-diastolic (EDD) and end-systolic diameter (ESD); stroke volume index ( SVI); cardiac index (CI); peripheral vascular resistance (PVR); left ventricle fractional shortening (FS) and ejection fraction (EF).

We detected a progressive reduction of MBP without any HR modification. MBP reduction was associated with a reduction of PVR and a parallel rise of CI and SVI. There was also an increase of FS and EF reflecting a reduced ESD. We conclude that PGI₂ infused in man at the rate stated above causes hypotension reflecting an arterial vasodilating effect; a lack of heart rate reflex response to afterload reduction (probably a nerve-mediated effect of PGI ); and no venous vasodilation, judging from the absence of any change in end-diastolic diameter.

Intra-jugular nanomole injections of leukotrienes B₄, C₄ and D₄ (LTB₄, LTC₄, LTD₄) in anesthetized guinea-pigs have been shown to cause dose-dependent increases of the mean arterial blood pressure. While the responses to LTB₄ were monophasic, the responses to LTC₄ and LTD₄ were characterized by a fast (10–50 sec), medium high, first pressor phase followed by a second, longer lasting (3–9 min), more important pressor phase. Like antigen-antibody reactions, leukotrienes induced cardiac effects such as tachycardia and rhythm disturbances as well as respiratory difficulties, convulsions and sometimes death of the animals. The prostaglandin synthesis inhibitor, indomethacin, reduced the pressor response and the tachyarrhythmic effects of LTB₄, C₄ and D₄. These results raise the possibility that leukotrienes produce their hemodynamic effects in guinea-pigs by stimulating the synthesis and release of biologically active derivatives of arachidonic acid.

The aggregation of human platelets is enhanced after preincubation with lithium salts. Previously it was shown that lithium inhibits adenylate cyclase activity in human platelets.

Enhancement of aggregation and inhibition of adenylate cyclase by lithium was not observed in rabbit platelets.

In this paper it is shown that in human platelets lithium enhances considerably the synthesis of thromboxane B₂, whereas the synthesis of PGE₂ and PGF_2α was enhanced to a lesser extent. In rabbit platelets lithium had no effect on prostaglandin synthesis. It is concluded that lithium specifically stimulates the synthesis of thromboxanes in human platelets, probably due to the previously reported inhibition of adenylate cyclase activity, resulting in an increased aggregability.

The contractile activity of uterine horns maintained for 90 to 120 minutes under normal oxygenation (carbogen or 100% O₂) became undetectable. When in this condition the gassing was stopped one or two minutes later, regular phasic contractions appeared super-imposed on a small increment of the basal resting tone. Indomethacin and aspirin well known inhibitors of prostaglandin (PG) synthesis, blocked the contractile influence of hypoxia whereas neither tranylcypromine or imidazole were able to alter the stimulatery action. PGE₂, PGE₁ and PGF_2α released into the bathing solution during 10 minutes of normoxia or 10 minutes of hypoxia, were measured. Under O₂, PGE₂ and PGF_2α production diminished significantly (P < 0.05 and P < 0.01, normoxia vs. hypoxia, respectively) whereas PGE₁ increased (P < 0.05). “PGI₂-like material” generated was also detected and it was found that the values during hypoxia were lower than those observed in 02; however the difference was not statistically significant. Dose-response contractile activity to PGs with and without gassing was explored. It was necessary to add 100 times more PGF_2α to obtain the minimal response under hypoxic conditions as compared to normoxia. On the other hand the threshold response to PGE₁ was 10 times lower under hypoxic conditions than in normoxia. The possible mechsnism(s) that induce an increment in PGE₁ generation accompanied by a simultaneous decrement of PGE₂ during hypoxia is discussed in connection with a possible role of PGE₁ evoking uterine contractions when the gassing of the suspending solution is stopped.

This study evaluated the effect of prostaglandin (PG) on renal function in normal and deoxycorticosterone-acetate (DOCA) hypertensive Yucatan miniature swine. Eight animals were implanted with DOCA impregnated silicone strips. MAP increased in the conscious DOCA animals from a normal pressure of 110–115 mmHg, to 148 ± 4 mmHg.After 3–4 weeks, the DOCA hypertensive and eight normal (sham or non-implanted) animals were anesthetized with sodium pentobarbital which reduced MAP in the DOCA pigs to normotensive levels. Under anesthesia, PG inhibition (indomethacin or meclofenamate, 2 mg/kg i.v.) increased MAP only in the normal group (P < .05). PG inhibition caused a significant reduction in renal blood flow in both groups, but only decreased glomerular filtration rate in the DOCA animals (P < .05). Radioactive microsphere distribution to the outer cortex of the normal animals was significantly decreased with PG inhibition, (P < .05). No consistant changes in electrolyte excretion or urine flow rate was seen in either group following PG inhibition. These data indicate that PG may influence renal hemodynamics in both normal and DOCA hypertensive Yucatan miniature swine. The finding that PG inhibition selectively decreases GFR in the DOCA animals suggests a possible protective role of these hormones in this hypertensive animal model.

Glycyrrhizin was found to inhibit prostaglandin E₂ production by activated rat peritoneal macrophages. Preincubation of the cells with glycyrrhizin increases its inhibitory effectiveness. Glycyrrhetinic acid, the aglycone of glycyrrhizin, at a dose of 100 μg per ml also inhibited prostaglandin E₂ production, but the inhibition was considered to be attributable to a toxic effect on the cells since more than 30% of the cells were detached from the dish during the 8 hr incubation period. In contrast, glycyrrhizin did not detach the cells from the dish at doses up to 3 mg per ml. Release of [³H]arachidonic acid from prelabeled cells was also inhibited by glycyrrhizin. It is likely that anti-inflammatory activity of glycyrrhizin depends at least in part on its inhibitory effect of the production of prostaglandin E₂.