Biomedical subjects

E R Serros

Publications and source records attributed to E R Serros.

6 recordsLinked to original sources

PubMed1985

Effect of indomethacin on proteinuria in rats with autologous immune complex nephropathy.

Although non-steroidal anti-inflammatory agents have been used to reduce levels of urinary protein excretion in patients with the nephrotic syndrome, the general usefulness of these drugs in proteinuric states remains unclear. The present study was designed to confirm the efficacy and to investigate some of the mechanism/s of action of non-steroidal anti-inflammatory agents in animals with proteinuria as the result of a single form experimental renal disease. Autologous immune complex nephropathy was produced in groups of Lewis rats by the administration of autologous tubular Fx1A antigen. After marked proteinuria developed, indomethacin (8 mg/kg/day) was administered orally to one group of animals for five days while a control group received only vehicle. The level of urinary protein excretion in the indomethacin treated animals was 420 +/- 198 mg/day compared to a level of 1180 +/- 306 seen in the untreated animals (p less than 0.05). When the indomethacin-treated and control animals were compared, the reduction in proteinuria could not be found to be associated with a change in the glomerular filtration rate, urine electrolyte or osmolar excretion rates, electron microscopic appearance of the glomerular basement membrane, or a change in the glomerular permeability to neutral dextran. Treatment of animals with either sodium salicylate or lower does of indomethacin (both of which resulted also in significant falls in urinary prostaglandin E excretion rates) failed to reduce the levels of proteinuria. Thus, indomethacin was capable of reducing the levels of protein excretion in rats with autologous immune complex nephropathy although the mechanism of action of this agent remains unclear.

Animals↗

PubMed1981

Effect of prostaglandin inhibition on glomerular filtration rate in normal and uremic rabbits.

Studies were performed to assess the effect of alterations in prostaglandin biosynthesis on glomerular filtration rate in rabbits with normal renal function and after surgical reduction of renal mass. In normal animals, the administration of either of two cyclo-oxygenase inhibitors resulted in a 53% reduction in urine prostaglandin E excretion, but no change in the creatinine clearance. Creatinine clearance rates were normal almost 71% lower in the uremic animals when compared to the animals with normal renal function. Despite the reduction in renal mass, urine prostaglandin E excretion rates in the uremic animals were over twice that seen in normal rabbits. When factored by either glomerular filtration rate or remaining renal mass, urine prostaglandin E excretion rates in uremic rabbits were compared to normal animals were increased more than 9-times and 40 times respectively. Administration of cyclo-oxygenase inhibitors in the uremic animals resulted in a 71% decrease in urine prostaglandin E excretion, unlike and non-uremic animals, a 53% fall in creatinine clearance. These findings suggest that intact renal prostaglandin biosynthesis is a necessary factor in the homeostatic adaptive mechanisms which maintain the glomerular filtration rate in animals with decreased renal mass.

Animals↗

PubMed1981

Prostaglandin-dependent polyuria in hypercalcemia.

The present experiments examined the role of prostaglandin biosynthesis in the increase in urine flow rate seen in rats with hypercalcemia induced by the administration of 1,25-dihydroxycholecalciferol. In a first group, rats receiving the vitamin D metabolite developed hypercalcemia, polyuria, and increased urine prostaglandin E excretion. Indomethacin resulted in a fall in urine prostaglandin E excretion. A second group was fluid restricted to ascertain whether increased thirst could be an etiologic mechanism of the polyuria. This resulted in a trivial fall in urine flow rate despite a fall in body weight and a rise in both urine and plasma osmolality. In a final group, prostaglandin inhibition restored the vasopressin sensitivity of the hypercalcemic kidney. Accordingly, the polyuria seen in hypercalcemic rats after the administration of 1,25-dihydroxycholecalciferol is associated with an increase in urine prostaglandin E excretion and can be reversed by inhibition of prostaglandin synthesis. In addition, this polyuria can occur independent of the thirst mechanism. Finally, there is evidence that the vasopressin resistance of the hypercalcemic kidney could be reversed by prostaglandin inhibition.

Animals↗

PubMed1980

Effects of alterations in urine flow rate on prostaglandin E excretion in conscious dogs.

The relationships between urinary prostaglandin E excretion and urine flow rate were evaluated in 11 conscious mongrel dogs during antidiuresis, maximal water loading, vasopressin administration during maximal water loading, and mannitol infusion. Urine flow rates between 0.21 and 15.1 ml/min were achieved. Urinary prostaglandin E excretion rates, determined by a membrane receptor assay, varied directly with urine flow rates (r = 0.908). Vasopressin administration (34--540 microU . kg-1 . min-1) resulted in a fall, rather than the expected rise, in urinary prostaglandin E excretion. When the concentration of prostaglandin E in the urine was plotted against urine flow rate, the demonstrated relationship appeared most consistent with passive diffusion. Mannitol infusion increased urine flow rates to levels comparable to the levels seen with maximal water loading but did not result in a fall in plasma osmolality. Urinary prostaglandin E excretion rates, however, were not distinguishable from those in the previous group. These data demonstrate that urinary prostaglandin E excretion rates are determined, to a great extent, by urine flow rate and that the significance of the interpretation of elevated excretion levels of these lipids in diuretic states may have to be reevaluated.

Animals↗

PubMed1980

Effect of prostaglandin inhibition on demeclocycline administration in conscious rats.

Studies were performed in conscious rats to evaluate the role of renal prostaglandin biosynthesis in demeclocycline-induced polyuria. Three groups of animals were evaluated. Group 1 animals received only the diluents used for both demeclocycline and indomethacin. Group 2 received demeclocycline (20 mg/kg/day) and the indomethacin diluent. Group 3 received both demeclocycline and indomethacin (10 mg/kg/day). After eight days of demeclocycline administration, urine flow rate increased in the group 2 animals from 15.1 +/- 2.1 to 31.1 +/- 5.1 ml/day. Indomethacin failed to alter the magnitude of demeclocycline-induced polyuria despite a 60% reduction in urine prostaglandin E excretion rats. These studies demonstrate that the concentrating defect induced by demeclocycline can occur independent of alterations in praostaglandin biosynthesis and suggest that a change in renal prostaglandin biosynthesis is not an etiologic factor in demeclocycline-induced polyuria.

Animals↗

PubMed1979

Variability in rates of urine prostaglandin E excretion.

Urine prostaglandin E excretion rates were determined by hepatic receptor assay in three groups of conscious animals. Although 24-hour urine collections gave reproducibly similar levels of prostaglandin E excretion rates, levels obtained with consecutive 20-minute urine collections were extremely variable despite no obvious changes in renal function. Since short urine collection periods are used frequently in physiologic studies, the significance of variations in prostaglandin excretion rates in these studies may have to be re-evaluated.

Animals↗