Prostaglandins, leukotrienes, and medicine最新文献

The effect of phenobarbital treatment on the synthesis of prostacyclin in coronary vascular microsomes was studied in Sprague Dawley rats. It was found that the treatment increased the synthesis of prostacyclin by nearly 100%. The treatment also resulted in an increase in HDL and a decrease in LDL in the serum. In vitro effects of HDL and LDL on the microsomal synthesis of prostacyclin showed that the synthesis was stimulated by HDL and inhibited by LDL. Hence it appears that the increase in prostacycle in synthesis resulting from phenobarbital treatment was at least partly due to increased level of HDL and decreased level of LDL in the serum.

Arterial plasma concentrations of thromboxane B₂ (TxB₂), prostaglandin F_2α (PGF_2α) and 6-keto-prostaglandin F_lα (PGF_1α) were measured during endotoxin-induced acute respiratory failure (ARF) in anesthetized 10–12 wk old pigs. A 4.5 hour (hr) infusion of endotoxin resulted in a biphasic pattern of ARF. Phase 1 (0–2 hr) was characterized by increased pulmonary artery pressure, pulmonary vascular resistance (PVR), and alveolar-arterial O₂ gradient (ΔA-aO₂), and decreased cardiac index (CI) and lung dynamic compliance (LDC). Following a return of PVR and CI values towards baseline, a second phase (2–4.5 hr) of deteriorating function occurred and was characterized by additional increases in PVR and ΔA-aO₂ and decreases in CI and LDC. Baseline (i.e., 0 hr) plasma TxB₂ concentrations were 241 ± 24 pg/ml; these values peaked at 0.5 hr (3228 ± 712 pg/ml) and declined to 1635 ± 453 pg/ml at 4.5 hr. Plasma concentrations of PGF_2α slowly increased from a baseline value of 154 ± 32 pg/ml to 2355 ± 738 pg/ml at 4.5 hr, while PGF_1α values increased from 54 ± 2 pg/ml at 0 hr to 503 ± 172 pg/ml at 4.5 hr. Time-matched control pigs showed no changes in pulmonary hemodynamics or in plasma TxB₂, PGF_2α or PGF_1α levels. These results indicate that cyclooxygenase products are increased during both phases of endotoxin-induced ARF in pigs.

Renal function deteriorates progressively in partially nephrectomized rats. This deterioration of renal function may be ameliorated by a diet either low in protein or high in linoleic acid. In the present experiment, partially nephrectomized rats were pair fed diets low in protein, high in linoleic acid or both low in protein and high in linoleic acid. Survival of renal function was most prolonged in rats fed a diet with both a low protein and high linoleic acid content; glomeruli from these animals demonstrated increased glomerular PGE₂ production. This additive effect may be mediated by increased production of the vasodilatory PGE₂ by glomeruli.

Intrauterine tissues from women at term of pregnancy metabolized arachidonic acid by way of lipoxygenase pathways that included 5-, 12-, and 15- lipoxygenases. The major lipoxygenase product formed by amnion obtained before labor was leukotriene B₄ and after labor was 12-hydroxyeicosatetraenoic acid (12-HETE). Chorion laeve and decidua vera synthesized predominantly 15-HETE at all times and placenta produced mainly 12-HETE. Trends existed for increased prostaglandin formation with labor by amnion, chorion laeve and decidua vera and for increased lipoxygenase product formation by chorion laeve, decidua vera and placenta. It is suggested that products of arachidonic acid metabolism by way of lipoxygenase and cyclooxygenase pathways play significant roles in the control of fetal and uteroplacental hemodynamics and the mechanism(s) of parturition.

Prostanoid production by rabbit choroid plexus (CP) and irisciliary body (ICB), and the effects of adrenergic agonists thereon, were studied in vitro. Immunoreactive prostaglandin (PG) E₂ was the major prostanoid released by both tissues; the output from ICB was some two orders of magnitude greater than from CP. Immunoreactive 6-keto PGF_1α and thromboxane (TX) B₂, the dehydration products of prostacyclin and TXA₂, respectively, were detected in smaller quantities.

Epinephrine stimulated the outputs of PGE₂ and 6-keto PGF_1α, but not of TXB₂, from both tissues.ICB responded to epinephrine concentrations of 10⁻⁴ and 10⁻⁵, while only 10⁻⁴ was effective in stimulating prostanoid synthesis in the CP. Phenylephrine, an adrenergic agonist, stimulated prostanoid output from the ICB, but not from the CP. It is concluded that adrenergic mechanisms stimulate the biosynthesis of prostanoids in the rabbit CP and ICB. The implications of such interactions to aqueous humor and cerebrospinal fluid dynamics, or to other processes in brain and ocular physiology, are discussed.

Experiments were carried out on non-working isolated rabbit hearts perfused by Tyrode solution: the effects of Taurine introduced into the coronary circulation were studied

• •

  - on the biosynthesis of the anti-thromboxane synthetase factor (“FATS”)

• •

  - and on the TXA2 and PGI2 synthetase activities of cardiac tissue.

The effects of Taurine were simultaneously studied on the biosynthesis of TXA2 and PGI2 $\text{in vitro}$.

Experiments performed under the adopted conditions have shown that

• •

  - $\text{in vitro}$ Taurine did not significantly modify the biosynthesis of TXA2 and PGI2

• •

  - $\text{ex vivo}$ Taurine did not change the biosynthesis of “FATS” but inhibited both TXA2 and PGI2 synthetase activities of the cardiac tissue: Taurine was more active on the TXA2 synthetase activity than on the PGI2 one.

Thus Taurine promoted the formation of vasodilator and antiaggregating PGI2 at the expenses of vasoconstrictor and proaggregating TXA2. This could at least partly explain the beneficial effects of Taurine in the physiopethology of the heart.

Recent studies with high frequency ventilation (HFV) have noted that HFV-induced increases in mean airway pressure leads to a marked cardiovascular depression, especially in cardiac output (CO).Aside from mechanical events a negative inotropic agent possibly prostaglandin in nature may also be involved. This study examined the possible involvement of thromboxane A₂ (TXA₂) in the HFV-induced cardiovascular deterioration. Chloralose-anesthetized mechanically-ventilated dogs were subjected to HFV 4, 10, and 20 mm Hg for 30 min. Some animals were also treated with imidazole (25 mg/Kg/hr) prior to HFV. Arterial levels of TXB₂ (stable metabolite of TXA₂) where monitored by radioimmunoassay. During HFV, tracheal pressure-related decreases in both CO and stroke volume (SV) were noted. Imidazole treatment significantly reduced the decrement in SV. Application of HFV resulted in variable changes in circulating TXB₂ levels. Overall, application of HFV did not result in a significant change from baseline levels.Furthermore there was no correlation between changes in CO and SV with changes in arterial TXB₂ concentration. These results do not support the hypothesis that hyperexpansion of the lungs during HFV causes the release of a cardiodepressant prostanoid.

Rats were exposed to cigarette smoke once daily for 4 to 8 weeks. Bronchoalveolar lavage fluid was obtained from each animal and assayed for immunoreactive PGE₂, TXB₂ and 6-Keto-PGF_1α.Significant increase in TXB₂ and decrease in PGE₂ and 6-Keto-PGF_1α release into bronchoalveolar fluid as a consequence of cigarette smoking were observed. These changes of arachidonate metabolites in lung alveoli may account in part for bronchoconstriction induced by cigarette smoking.

We hypothesized that sulfidopeptide leukotrienes (LTC₄, LTD₄, LTE₄) might be important to the pathophysiology of endotoxin-induced acute respiratory failure (ARF) observed in young pigs. We used radioimmunoassay (RIA), reverse-phase high performance liquid chromatography (RP-HPLC) and guinea pig ileum bioassay techniques to determine the presence of sulfidopeptide leukotrienes in bronchoalveolar lavage fluid (BALF) and plasma of saline(n=12)- and endotoxin(n=12)-treated pigs. Endotoxin, infused at 5 μg/kg for 1 hr followed by 2 μg/kg/hr for 3.5 hrs, caused pulmonary hypertension, a biphasic increase in systemic and pulmonary vascular resistances, hypoxemia, bronchoconstriction and hemo-concentration. The levels of immunoreactive sulfidopeptide leukotrienes were not significantly increased in BALF recovered from endotoxemic pigs. Arterial plasma samples (collected at 0.5 hr intervals for 4.5 hrs) were below the detectable limits of the RIA. During RP-HPLC, ethanol extracted BALF failed to show an ultraviolet (UV) absorbance peak (280 nm) that was coincident with authentic standards. Concentrated BALF samples and BALF eluate fractions (collected at a retention time consistent with authentic LTC₄) failed to cause a sustained contraction of guinea pig ileum. We conclude that sulfidopeptide leukotrienes are not increased in BALF or plasma recovered from endotoxemic pigs and that these lipoxygenase metabolites might not be important factors contributing to the pathophysiology of endotoxin-induced ARF. An alternate explanation is that the sulfidopeptide leukotrienes are rapidly metabolized so as to be undetectable by the methods employed.