Prostaglandins and medicine最新文献

We have found a correlation between the activity of the PGI₂ synthetase in the microsomal fraction of pig aorta and the amount of high density lipoprotein (HDL) cholesterol in the incubation fluid. The reverse was true for low density lipoprotein (LDL) cholesterol. These correlations exist independently of whether the lipoproteins were isolated from men than from women as it is for HDL isolated from women than from men. This result may give an explanation for the differential risk against the incidence of cardiovascular diseases between women and men at the same concentration of the individual lipoproteins in their blood.

The present investigation has evaluated the effects of low doses of oral aspirin on platelet prostaglandin synthesis and function. Whole (80 mg) or half (40 mg) tablets of baby aspirin given to adults had no effect on the response of their platelets to thrombin, ADP and epinephrine, but selectively inhibited aggregation induced by threshold concentrations of arachidonate 16–20 hours after ingestion. Larger amounts of arachidonate overcame the inhibition imposed by low dose aspirin, but not by adult aspirin tablets (600 mg). Epinephrine, in concentrations too low to cause aggregation, restored the sensitivity of aspirin-treated platelets to arachidonate. Studies with a-adrenergic agonists, antagonists and calcium channel blockers demonstrated that the corrective effect of epinephrine was mediated by an a-adrenergic receptor influence on calcium modulation of the platelet membrane.

Intravenous infusion of carboprostacyclin, a chemically stable analogue of prostacyclin (PGI₂) resulted in ex-vivo inhibition of ADP-induced platelet aggregation at doses that did not produce significant changes in blood pressure or heart rate. Oral administration of relatively large doses of this compound also inhibited ex-vivo ADP-induced platelet aggregation but this was accompanied by headache, facial flush, tachycardia and changes in blood pressure.

Perfusion effluent from isolated rat and hamster lungs caused a relaxation of superfused strip of bovine coronary artery (BCA). This relaxation was abolished by pulmonary infusion of indomethacin. Pre-exposure of rats and hamsters to cigarette smoke during half an hour before the lung perfusion did not change the degree of this initial relaxation of BCA. Injection of 10 μg of sodium arachidonate (AA) into the pulmonary circulation of isolated hamster lungs caused a contraction of BCA, which was not changed by cigarette smoke pre-exposure. When AA (10 μg) was injected into the pulmonary circulation of isolated hamster lungs during cigarette smoke ventilation the contractions of superfused BCA and rat stomach strip (RSS) were not significantly different from those during the preceding and following air ventilation. In experiments with isolated rat lungs the initial relaxation of superfused BCA was accompanied by a contraction of superfused RSS. AA injection (10 μg) into rat lungs caused a further relaxation of BCA and contraction of RSS, which were abolished by pulmonary infusion of indomethacin. Cigarette smoke ventilation of isolated rat lungs caused a relaxation of superfused BCA, which was not abolished by indomethacin. During cigarette smoke ventilation injection of AA (10 μg) into the pulmonary circulation of rat lungs caused a relaxation of BCA and a contraction of RSS.

The present study indicates that neither cigarette smoke ventilation nor pre-exposure to cigarette smoke has a drastic effect on the metabolism of arachidonic acid to myotropic compounds in isolated hamster and rat lungs.

Intralipid-related pulmonary alterations have been attributed to hyperlipemia. To better quantitate and explain these alterations, Intralipid (0.4 gm/kg over one hour) was infused into three groups of rabbits and saline into a fourth group. Group I had normal lung function; Groups II-IV were pretreated with oleic acid and Group III also received indomethacin. Serum triglyceride (TG) levels, arterial (a) and end-tidal (A) PC0₂ and P0₂ were measured at baseline and then hourly for six hours. There was no ventilatory deterioration in Group I despite a peak TG level of 638 mg/dl. In Group II there was an Intralipid-related Pa0₂ decrease of 11–13 mmHg(p < .01)and aΔ AaP0₂ increase of 16 mm Hg (p < .O1); both returned to baseline without significant TG normalization. Since indomethacin prevented these Pa0₂ and Δ AaP0₂ changes despite a significant TG increase, the effects of Intralipid appear not to be TG-related but rather to be related to PG-mediated alterations in pulmonary vasomotor tone. Our results are most consistent with a net increase in vasodilating prostaglandins and resultant hypoxemia secondary to unblocking of baseline hypoxic vasoconstriction.

Indomethacin treatment (3–8 daily doses of 100 mg) to patients resulted in an increased level of peripheral blood monocytes, as compared to the initial values measured in each individual subject before taking the drug. Normal levels were resumed after the treatment stopped. The idea that these observations were related to the drug treatment per se and not superimposed by the arthritis was verified by the fact that similar results were obtained in healthy volunteers taking this drug.

The ability of various human and ovine blood plasmas to inhibit prostaglandin synthesis $\text{in vitro}$ has been tested. Human plasmas were significantly more potent in their ability to inhibit prostaglandin synthesis than their counterpart ovine plasmas. In general, female plasma had greater inhibitory activities than male plasmas and adult plasmas were more active than fetal plasmas. There was no simple correlation between the activity of plasmas as inhibitors of prostaglandin synthesis and their respective albumin or haptoglobin contents.

The effects of 6-keto-PGE₁ on aggregatory responses to arachidonic acid (AA), adenosine diphosphate (ADP) and collagen were studied in human platelet-rich plasma (PRP). In addition, experiments were carried out to determine if these effects correlate with changes in platelet cyclic AMP and cyclic GMP levels. 6-Keto-PGE₁ incubated in PRP produced dose-related increases in platelet cyclic AMP levels whereas platelet cyclic GMP levels were unchanged. Control aggregations induced by AA and ADP did not alter cyclic AMP and cyclic GMP levels whereas control aggregations induced by collagen elevated cyclic GMP levels while cyclic AMP levels were unchanged. 6-Keto-PGE₁ produced a dose-dependent inhibition of platelet aggregation induced by AA, ADP and collagen and this inhibition correlated with a dose-related increase in cyclic AMP levels. Since 6-keto-PGE₁ does not consistently alter cyclic GMP levels in human PRP, the present data support previous studies suggesting that 6-keto-PGE₁ produces inhibition of platelet aggregation through the stimulation of cyclic AMP accumulation.