2-3-dinor-6-ketoprostaglandin-f1alpha and Body-Weight

This multicenter, double-blind, randomized, placebo-controlled, parallel-group study assessed renal function during dosing with etoricoxib 90 mg daily, celecoxib 200 mg twice daily, and naproxen 500 mg twice daily. Male and female subjects 60 to 81 years old (n = 85), in sodium balance on a controlled, normal sodium diet, were treated for 15 days. There were no clinically meaningful between-treatment differences in urinary sodium excretion, creatinine clearance, body weight, or serum electrolytes during the 2 weeks of treatment. Etoricoxib and celecoxib had no effect on the urinary thromboxane metabolite, 11-dehydrothromboxane B(2), while significantly decreasing the urinary prostacyclin metabolite, 2,3-dinor-6-keto PGF(1alpha). Decreases were greater for both metabolites following naproxen. Ambulatory systolic blood pressures were significantly higher than placebo for all treatments, with moderately greater increases for etoricoxib relative to other active treatments on day 14. Ambulatory diastolic blood pressures were significantly higher than placebo for etoricoxib and naproxen but not for celecoxib.

Topics: 6-Ketoprostaglandin F1 alpha; Administration, Oral; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Blood Pressure; Body Weight; Celecoxib; Constipation; Creatinine; Diarrhea; Dose-Response Relationship, Drug; Double-Blind Method; Electrolytes; Etoricoxib; Female; Headache; Humans; Male; Middle Aged; Naproxen; Potassium; Prostaglandins; Pyrazoles; Pyridines; Sodium; Sulfonamides; Sulfones; Thromboxane B2

In addition to a variety of lipids, 2 products of the arachidonic acid cascade, prostacyclin and thromboxane, are involved in the pathogenesis of atherosclerosis as a result of their effects on platelet function and on the vascular endothelium. The aim of the present investigation was to ascertain if a sub-maximal 8 week endurance training period followed by a 4 week detraining period would have any effects on high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglycerides (TG), 2,3-dinor-6-keto-prostaglandin F(1alpha) (2,3-dinor-6-keto-PGF(1alpha)), the urinary metabolite of prostacyclin, 2,3-dinor-thromboxane B2 (2,3-dinor-TXB2), the urinary metabolite of thromboxane, and the ratios of TC to HDL-C and of 2,3 dinor-6-keto-PGF(1alpha) to 2,3-dinor-TXB2. Thirty-eight boys aged 10-14 were randomly divided into exercise (n = 21) and control (n = 17) groups. The exercise group trained on a bicycle ergometer 4 times/week, 1 h/session, at 80% of their physical working capacity at a heart rate of 170 beats/min (PWC(170)), for 8 weeks. The control group did not participate in any specific physical exercise program. The results showed that relative to the control group, the exercise group had a significant increase in HDL-C and 2,3-dinor-6-keto-PGF(1alpha) concentrations at the end of the 4th (p < 0.05 and p < 0.001, respectively) and the 8th week (p < 0.01 and p < 0.001) of training, respectively; a significant increase in the 2,3 dinor-6-keto-PGF(1alpha) - 2,3-dinor-TXB2 ratio (p < 0.05 and p < 0.01 at the same intervals); a significant decrease in TG at the end of the 8th week of training (p < 0.05); and a significant decrease in the TC--HDL-C ratio at the end of the 4th (p < 0.05) and 8th weeks of training (p < 0.001).

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Arachidonic Acid; Body Weight; Child; Cholesterol; Cholesterol, HDL; Heart Rate; Humans; Lipids; Longitudinal Studies; Male; Physical Endurance; Physical Exertion; Physical Fitness; Thromboxane B2; Triglycerides

The renin-angiotensin system plays a critical role in cardiovascular function, but little is known about the effects of specific cyclooxygenase 2 (COX-2) inhibition on this system in healthy humans under physiologic conditions.. Twenty-one healthy female volunteers received, in a randomized, double-blind, crossover study, celecoxib 200 mg twice a day, indomethacin 50 mg three times a day, or placebo for 4 days and a single dose, each, on day 5. On day 5 of each treatment, the following parameters were assessed with subjects in an upright position before and after administration of 20 mg furosemide intravenously: plasma renin activity (PRA), plasma aldosterone, serum and urine electrolytes, and creatinine. Index metabolites of prostanoids were analyzed by gas chromatography-tandem mass spectrometry in 24-hour urine on day 4 and in 2-hour urines before and after furosemide administration.. Baseline and furosemide-stimulated PRA were reduced to a similar degree by celecoxib and indomethacin. Plasma aldosterone and urinary excretion of potassium showed changes consistent with the alteration of PRA. Urinary excretion rates of prostaglandin E(2), (PGE(2)), 7alpha-hydroxy-5, 11-diketotetranor-prosta-1,16-dioic acid (PGE-M), and 2,3-dinor-thromboxane B(2) (TxB(2)) were not reduced by celecoxib, whereas indomethacin led to a decrease of 40%, 45%, and 80%, respectively. Both active treatments inhibited urinary excretion of 2,3-dinor-6-keto-PGF(1alpha) and 6-keto-PGF(1alpha) by 60% and 40%, respectively.. Renin-release in healthy humans with normal salt intake is COX-2 dependent. While COX-1 is critical for renal and systemic PGE(2) production, renal prostacyclin synthesis is apparently COX-2 dependent. Finally, the previously demonstrated shift of the thromboxane-prostacyclin balance toward prothrombotic thromboxane by specific COX-2 inhibition is confirmed.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aldosterone; Body Weight; Celecoxib; Creatinine; Cross-Over Studies; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprostone; Diuretics; Female; Furosemide; Humans; Indomethacin; Kidney; Potassium; Prostaglandins; Pyrazoles; Renin; Sodium; Sulfonamides; Thromboxane B2

The effects of exercise training on eicosanoid levels were studied in male Wistar rats. One-month-old rats were trained on a drum exerciser at an intensity of around 70% of maximal oxygen consumption for 10 weeks (60 min day-1, 5 days week-1) after familiarization. Some animals of the same age did not exercise and served as a control. Two days after training, several blood vessels, including thoracic aortae, inferior vena cavae, external iliac arteries, external iliac veins, common carotid arteries and jugular veins, were excised and incubated for 10 min. Basal release of prostacyclin from these vessels was determined using [125I]radio-immunoassay (RIA) of 6-keto-PGF1 alpha. The levels of plasma prostacyclin and urinary metabolites of prostacyclin and thromboxane were also determined by RIA. Our results showed that trained animals had lower body weight and urine 11-dehydro-thromboxane B2 levels than the controls (P < 0.001 and P < 0.05, respectively). In contrast, urinary 2,3-dinor-6-keto-PGF1 alpha level was elevated after training (P < 0.05). Nonetheless, prostacyclin levels in plasma and from various dissected vessel segments, except thoracic aorta, did not change significantly after training. These findings suggest that exercise training may affect endogenous eicosanoid levels by increasing the basal release of prostacyclin and reducing the basal thromboxane level.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Blood Cell Count; Body Weight; Epoprostenol; Male; Muscle, Smooth, Vascular; Oxygen Consumption; Physical Exertion; Pulmonary Gas Exchange; Rats; Rats, Wistar; Thromboxane B2; Thromboxanes