Prostaglandins最新文献

The effects of iloprost infusion (100ng/kg/min for 75 min) alone and in combination with aspirin (3mg/kg IV bolus) were compared in a canine model of myocardial reperfusion injury. Regional ischemia of 40 min was produced by temporary occlusion of the left anterior descending coronary artery, after which the myocardium was reperfused for a period of 3 hours. Mean arterial pressure (MAP), heart rate (HR), left ventricular end diastolic pressure (LVEDP), positive (+) LVdP/dt_max and negative (−) LVdP/dt_max were monitored. Rate pressure product and (−) dP/dt/P_max were also derived from the above. Myocardial tissue levels of adenosine triphosphate (ATP), creatine phosphate (CP), glycogen and lactate were estimated. Following reperfusion in the saline treated group, there was a significant fall in (i) MAP, (ii) (+) LVdP/dt_max and (iii) (−) LVdP/dt_max. LVEDP was corrected about 2 hours after reperfusion. Despite correction of lactate accumulation, ATP and glycogen were not restored although the CP store was replenished.

The hemodynamic profiles in both iloprost and in combination treated groups were similar; (i) depressed MAP (particularly during iloprost infusion) without any significant change in HR (ii) no significant depression in (+) LVdP/dt_max (iii) depression in (−) LVdP/dt_max but not when corrected for lower P_max and (iv) a significant reduction in the incidence of reperfusion arrhythmias. Similarly, in both the drug/s treated groups, ATP, CP and lactate were normalised although glycogen store was not restored. The results of this study indicate (i) cardioprotective effect of iloprost even when administered prior to reperfusion and (ii) no additional protective effect of combining iloprost and aspirin.

In vivo administration of HOE 140 (a new bradykinin receptor antagonist) and L-NAME (Nitric oxide synthase inhibitor) was performed in chronic streptozotocin-diabetic rats. Basal increases (in umol.g dw⁻¹) in liver (45.0 ± 3.4.1) and uterine (40.0 ± 2.95) triglyceride levels in diabetic animals vs control (liver: 34.0 ± 3.87; uterus: 30.2 ± 4.01) were partially prevented by L-NAME (p < 0.01), HOE 140 (p < 0.01) and L-NAME + HOE 140 (p < 0.01). High glycogen levels (in mg.g dw⁻¹) observed in diabetic uterine tissue (3.07 ± 0.90), and decreased glycogen content detected in diabetic liver (11.64 ± 1.50) vs. control (uterus: 1.59 ± 0.15; liver: 17.25 ± 0.87) were unaffected. Uterine ¹⁴CO₂ production from ¹⁴C-U-Glucose (in uCi.mg dw), which is lower in diabetic (35.0 ± 5.12) than in control (50.12 ± 4.54) tissues, was improved by HOE 140 (p < 0.05) and L-NAME + HOE 140 (p < 0.05), while hepatic glucose oxidation was not increased by the drugs. Glycemia levels were decreased in diabetic rats injected with L-NAME and L-NAME plus HOE 140.

Pancreatic 6-Keto-prostaglandin F_1alpha to Thromboxane B₂ ratio was lower in diabetic animals than in controls, and L-NAME and/or HOE 140 treatment prevented the decrement. These findings suggest that vasoactive compounds might prevent streptozotocin-induced damage in pancreatic tissue from chronic diabetic rats.

We demonstrated the effect of epidermal growth factor (EGF) on the production of PGE₂ in human squamous carcinoma A431 cells. The production of PGE₂ was increased by stimulating the cells with EGF for 2 h and reached a maximum for 10 h. EGF was also found to augment the release of arachidonic acid (AA) following the increase in phospholipase A₂ (PLA₂) activity (1.7-fold). The induced PLA₂ activity was diminished by 4-bromophenacyl bromide, but not by dithiothreitol, indicating that the EGF-induced release of AA was due to the increase in the activity of cytosolic PLA₂ (cPLA₂). On the other hand, cyclooxygenase (COX) activity was increased (1.6-fold) within 2 h after the EGF-treatment and the induced activity was inhibited by cycloheximide. In addition, Northern blot analysis showed that the level of COX-2 mRNA was increased by the EGF-treatment, whereas no COX-2 mRNA was detected in the untreated cells, indicating that the EGF-induced COX activity was resulted from the increase in the production of COX-2. These results suggest that EGF augments the production of PGE₂ by increasing not only the activity of cPLA₂ but also the production of COX-2 in A431 cells.

Secretion of progesterone $\text{in vitro}$ by mature day 8 ovine corpora lutea (CL) of the estrous cycle was increased linearly by ovine LH (1, 10 and 100 ng/ml) or prostaglandin E₂ (PGE₂) 1, 10 and 100 ng/ml) in a dose dependent manner (P ≤ 0.05). Progesterone secretion $\text{in vitro}$ by 88–90 day ovine CL of pregnancy was not affected P ≥ 0.05 by LH (1, 10 and 100 ng/ml) while prostaglandin E₁ (PGE₁) 1, 10 and 100 ng/ml) increased (P ≤ 0.05) secretion of progesterone in a dose dependent manner and PGE₂ (1, 10 and 100 ng/ml) increased (P ≤ 0.05) secretion of progesterone only at the 100 ng/ml dose. Day 8 ovine CL of the estrous cycle did not secrete (P ≥ 0.05) detectable quantities of prostaglandin F₂α (PGF₂α) or prostaglandin E (PGE) while 88–90 day ovine CL of pregnancy secrete PGE (P ≤ 0.05) but not PGF₂α (P ≥ 0.05).

Regulation of PGE secretion by 88–90 day ovine CL of pregnancy may be via pregnancy specific protein B (PSPB), which increased (P ≤ 0.05) PGE and progesterone but not PGF₂α (P ≥ 0.05) secretion. Secretion of progesterone by CL of 88–90 days of pregnancy was not affected by IGF₁, IGF₂, PAF-16, PAF-18, oxytocin, PGI₂, PGD₂ or leukotriene C₄ (P ≥ 0.05). It is concluded that PGE₁ or PGE₂ but not LH regulates secretion of progesterone $\text{in vitro}$ by 88–90 day ovine CL of pregnancy. In addition, it is concluded that 88–90 day ovine CL of pregnancy secretes it's own luteotropin, which is PGE. Secretion of PGE by ovine CL of pregnancy may be regulated by PSPB.

The purpose of this study was to assess the anti-platelet properties of endocardial endothelial cells (EECs) by measuring platelet aggregation after a brief incubation with cultured EECs. EECs were isolated from the right ventricles of porcine hearts and coronary artery endothelial cells (C-ECs) were also isolated from the same animals. After brief incubations (2-min) of platelet suspensions with cultured EEC and C-EC monolayers, platelet aggregation in response to thrombin and 6-keto-PGF_1α (a stable metabolite of PGI₂) content of platelet suspensions were measured. Platelet aggregation was significantly inhibited by a brief incubation of platelet suspensions with EEC and C-ECs monolayers. Pretreatment of EECs and C-ECs with indomethacin (5 × 10⁻⁵ M) restored platelet activity, but pretreatment with N^ω-nitro-L-arginine methyl ester (L-NAME; 5 × 10⁻⁵ M) or hemoglobin (1 × 10⁻⁶ M) did not. Platelet/EEC interactions multiplicatively increased the 6-keto-PGF_1α content of platelet suspensions and the 6-keto-PGF_1α content of platelet suspensions after incubations with EECs correlated significantly with the inhibition of platelet aggregation. Both the anti-aggregation properties and 6-keto-PGF_1α production were significantly greater in EECs than in C-ECs. A brief incubation (2-min) with PDGF (10 ng/ml) or TGF-β (1 and 10 ng/ml) stimulated 6-keto-PGF_1α production in EECs but not in C-ECs, although these growth factors stimulated 6-keto-PGF_1α production in C-ECs after a longer incubation time (30 or 60 min). In this study, after a brief incubation (2-min) with platelet suspensions, EECs inhibited platelet aggregation mainly through the release of PGI₂ but not EDRF. As this anti-aggregation property was significantly greater in EECs than in C-ECs, it is suggested that endocardial endothelial PGI₂ may inhibit both intracardiac and intracoronary artery thrombus formation, contributing to the prevention of myocardial ischemia.

We examined whether beraprost sodium (beraprost), a stable analogue of PGI₂, has an anti-inflammatory effect on the permeability barrier through endothelial cells in vivo. The injection of collagen (5 μg/head) plus epinephrine (0.6 μg/head) showed time-dependently the increased Evans blue dye leakage of the lung in mice for 60 min. Beraprost significantly suppressed this leakage dose-dependently (control; 11.26 ± 1.64 μg/lung, beraprost 10 μg/kg; 7.49 ± 1.36 μg/lung, 30 μg/kg; 5.33 ± 0.71 μg/lung, 100 μg/kg; 5.52 ± 0.79 μg/lung). Pulmonary thromboembolism-induced Evans blue dye leakage was also reduced significantly by aspirin (5 mg/kg), but PGE₁ (170 μg/kg) showed a tendency to potentiate the edematogenic response. One week after the injection of same dosage of collagen plus epinephrine in mice, pulmonary thromboembolism showed the increase of wet-to-dry weight ratio of the lung (normal; 3.84 ± 0.01, control; 3.96 ± 0.04) and right ventricular hypertrophy (normal; 28.2 ± 0.9%, control; 32.3 ± 0.9%) compared to normal mice. Beraprost significantly suppressed lung edema and hypertrophy dose-dependently, and over 30 μg/kg/day of beraprost, the effects were statistically significant (beraprost 30 μg/kg/day; 3.85 ± 0.02 and 27.8 ± 1.4%, 100 μg/kg/day; 3.85 ± 0.02 and 27.3 ± 1.1%). Beraprost significantly reduced 5-hydroxytryptamine (5-HT; 17 nmol/paw)-induced rat paw edema dose-dependently (5-HT alone; 100%, beraprost 10⁻¹³ mol/paw; 91.19 ± 2.22%, 10⁻¹² mol/paw; 85.79 ± 4.85%, 10⁻¹¹ mol/paw; 78.49 ± 3.95%). 5-HT-induced edema was also suppressed significantly by the co-injection of (−)-isoproterenol (10⁻¹² mol/paw), but PGE₁ (10⁻¹¹ mol/paw) significantly potentiated the edematogenic response. From these results, we propose that the anti-inflammatory effect of beraprost may be contributed, in part, to the permeability barrier through end othelial cells in vivo. © 1997 by Elsevier Science Inc.