dinoprost and Diabetes-Insipidus

It is known that n-3 polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid and eicosapentaenoic acid, are rapidly oxidized in vitro. Nvarepsilon-(propanoyl)lysine (propionyllysine, or PRL) is formed from the reaction of the oxidized products of n-3 PUFAs and lysine. To evaluate the oxidized n-3 PUFA-derived protein modifications in vivo, we have developed detection methods using a novel monoclonal antibody against PRL as well as liquid chromatography-mass spectrometry (LC/MS/MS). The antibody obtained specifically recognized PRL. A strong positive staining in atherosclerotic lesions of hypercholesterolemic rabbits was observed. We have also simultaneously identified and quantified both urinary PRL and urinary Nvarepsilon-(hexanoyl)lysine, using LC/MS/MS using isotope dilution methods. The level of urinary PRL (21.6+/-10.6 micromol/mol of creatinine) significantly correlated with the other oxidative stress markers, 8-oxo-deoxyguanosine, dityrosine, and isoprostanes. The increase in the excretion of amide adducts into the urine of diabetic patients was also confirmed compared to healthy subjects. These results suggest that PRL may be good marker for n-3 PUFA-derived oxidative stress in vivo.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antibodies, Monoclonal; Aorta; Biomarkers; Coronary Artery Disease; Deoxyguanosine; Diabetes Insipidus; Dinoprost; Fatty Acids, Unsaturated; Humans; Hypercholesterolemia; Immunochemistry; Lysine; Mass Spectrometry; Oxidation-Reduction; Oxidative Stress; Propionates; Rabbits

A case of familial central diabetes insipidus and dilatation of the urinary tract is reported. Administration of desmopressin for 1 year improved urinary tract dilatation with a concomitant reduction in urine volume. Urinary cyclic adenosine monophosphate and prostaglandin E2 excretion increased after treatment.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Cyclic AMP; Deamino Arginine Vasopressin; Diabetes Insipidus; Dinoprost; Dinoprostone; Humans; Hydronephrosis; Male; Thromboxane B2; Urine

1. The production of prostaglandin (PG) E2, F2 alpha and thromboxane B2 (TXB2) by isolated glomeruli, cortical tubular suspensions and medullary and papillary slices was measured in normal Long-Evans rats 4, 8 and 14 days after starting on oral Na+ load and the results were compared with those of rats on a normal Na+ intake. 2. In glomeruli, PGE2 decreased at days 4 and 8, and returned to normal at 14 days. PGF2 alpha decreased only at day 4 and TXB2 decreased in all Na+-loaded animals. In cortical suspensions, a transient decrease of PGE2 was observed at day 4. In medullary slices, PGE2 and TXB2 decreased in all experimental periods. In contrast, in papillae, a significant increase of PGE2 was observed with Na+ loading at day 8, but PGF2 alpha and TXB2 did not change consistently. 3. Similar changes were observed in rats with hypothalamic diabetes insipidus (DI rats) Na+ loaded for 4 days, as compared with DI rats on a normal Na+ intake. 4. The results suggest that prostanoids participate in the renal adaptation to an increased Na+ intake, and that this response is relatively independent of the presence of antidiuretic hormone.

Topics: Animals; Diabetes Insipidus; Dinoprost; Dinoprostone; Female; Kidney; Prostaglandins; Prostaglandins E; Prostaglandins F; Rats; Sodium; Thromboxane B2; Time Factors; Tissue Distribution

Current evidence suggests that the antidiuretic hormone (ADH) and changes in sodium balance influence renal prostaglandins (PGs). To separate these two mechanisms, the effect of sodium loading on the urinary excretion of PGE2 and PGF2 alpha was studied in female Brattleboro rats with diabetes insipidus (DIHO) and compared with that in female, age matched, heterozygous Long Evans controls (LEHE). Ten DIHO and ten LEHE rats had a normal sodium intake. In ten DIHO rats a 0.16% NaCl solution was supplied instead of drinking water for either 8 days (n = 5) or 14 days (n = 5). In two groups of LEHE rats, sodium loading was obtained with a 0.80% NaCl solution for the same study periods. Urine PGs were measured by radioimmunoassay in three 24 h urine collections for each rat. Urine PGs were significantly increased in the 8 day loaded but not in the 14 day loaded LEHE rats. In DIHO rats, a non-significant increase in both PGE2 and PGF2 alpha was present after 8 days of sodium loading, while PGE2 and the E/F ratio were decreased after 14 days of salt loading. The findings suggest that the natriuresis induced by sodium loading in the rat may be mediated in part by increased production of PGs. In addition, it seems that ADH plays a role in this response.

Topics: Animals; Diabetes Insipidus; Dinoprost; Dinoprostone; Female; Potassium; Prostaglandins E; Prostaglandins F; Rats; Rats, Brattleboro; Rats, Inbred Strains; Sodium; Sodium Chloride

In order to assess the relative roles played by potassium (K) and the antidiuretic hormone (ADH) on the renal production of prostaglandins (PG) E2 and F2 alpha, the 24 hour urinary excretion of these substances was measured in Brattleboro rats (devoid of ADH) and in control Long Evans heterozygote rats. Rats of each strain received either a normal K intake or a K load for 8 days. Urinary PGE2 and PGF2 alpha were measured by radioimmunoassay in three consecutive 24 h urine collections obtained after the above periods. K loading induced an increase in PGF2 alpha (p less than 0.01), PGE2 showing a non significant trend to decrease. The E/F ratio was decreased in K loaded animals. The changes were qualitatively similar in presence or absence of ADH, but animals with diabetes insipidus had lower levels of PGs than control animals. The results suggest the possibility that K loading induces an increase in the activity of the renal enzyme PGE2-9-ketoreductase. The resulting increase in PGF2 alpha could play a role in K excretion and this response is probably independent of ADH.

Topics: Animals; Diabetes Insipidus; Dinoprost; Dinoprostone; Female; Hydroxyprostaglandin Dehydrogenases; Kidney; Potassium; Prostaglandins E; Prostaglandins F; Rats; Rats, Brattleboro; Rats, Mutant Strains; Vasopressins; Water-Electrolyte Balance

The results of estimation of renal prostaglandin (PG) excretion showed a significantly decreased excretion of PGE2 by 71% and that of PGF2 alpha--by 28% in rats with hereditary diabetes insipidus (DI), compared to the control Long Evans (LE) rats. The results suggested an inhibition of renal PG synthesis in DI rats due to the absence of stimulatory effect of ADN in DI rats lacking ADH. An inverse correlation between plasma renin activity and renal PG excretion was found (r = --0.36). The renal kallikrein excretion of DI rats was not significantly different compared to that of LE rats. An attempt for explanation of these results was made.

Topics: Animals; Diabetes Insipidus; Dinoprost; Dinoprostone; Kallikreins; Kidney; Kinins; Male; Prostaglandins; Prostaglandins E; Prostaglandins F; Rats; Rats, Brattleboro; Renin-Angiotensin System

To define the importance of renal prostaglandins in nephrogenic diabetes insipidus (NDI), diuresis and the urinary excretion of PGE2 and PGF2 alpha were studied in a patient with NDI before and during inhibition of endogenous prostaglandin synthesis with either indomethacin (IND) or acetyl-salicylic acid (ASA). The excretion rates of PGE2 and PGF2 alpha were in the low normal range for the patient's age group, remained unchanged during 6 h of fluid deprivation and were suppressed by IND (150 mg/day), ASA (3 g/day), and by the combination of IND and hydrochlorothiazide (HCT, 50 mg/day). However, whereas IND, HCT, and the combination of IND and HCT reduced diuresis ASA did not. Free water clearance as determined during fluid deprivation remained positive during each phase of therapy. These data fail to demonstrate a direct effect of endogenous ADH on renal prostaglandin synthesis in NDI. The ineffectiveness of ASA to reduce diuresis indicates that indomethacin affects diuresis in NDI by a mechanism other than inhibition of cyclooxygenase.

Topics: Adolescent; Aspirin; Diabetes Insipidus; Diabetic Nephropathies; Dinoprost; Dinoprostone; Diuresis; Drug Therapy, Combination; Female; Humans; Hydrochlorothiazide; Indomethacin; Male; Osmolar Concentration; Prostaglandins E; Prostaglandins F; Sodium; Thirst; Vasopressins

Topics: Animals; Diabetes Insipidus; Dinoprost; Dinoprostone; Diuresis; Female; Prostaglandins E; Prostaglandins F; Rats; Rats, Brattleboro; Water-Electrolyte Balance

The renal response to arginine vasopressin was investigated with and without the simultaneous administration of the kallikrein inhibitor, aprotinin, in conscious Brattleboro homozygous rats with hereditary diabetes insipidus. Arginine vasopressin caused a marked antidiuretic response (urinary osmolality increased from 118 to 739 mosmol/l) which was accompanied by a significant increase in urinary prostaglandin excretion (prostaglandin E2 and F2 alpha excretion increased by 182 and 441%, respectively). Kallikrein excretion remained unchanged after arginine vasopressin infusion. The infusion of aprotinin diminished urinary kallikrein activity to undetectable levels, decreased potassium excretion significantly and caused a slight fall in urinary prostaglandin excretion. However, aprotinin failed to modify the arginine vasopressin-induced enhancement in prostaglandin excretion (prostaglandin E2 and F2 alpha excretion increased by 168 and 442%, respectively), and the antidiuretic response was also similar to that observed under control conditions. These results indicate that the kallikrein-kinin system is not involved in the renal response to vasopressin in the Brattleboro rat.

Topics: Animals; Aprotinin; Arginine Vasopressin; Diabetes Insipidus; Dinoprost; Dinoprostone; Diuresis; Female; Kallikreins; Kidney; Osmolar Concentration; Prostaglandins E; Prostaglandins F; Rats; Rats, Brattleboro

Topics: Animals; Arginine Vasopressin; Aspirin; Deamino Arginine Vasopressin; Diabetes Insipidus; Dinoprost; Dinoprostone; Enzyme Induction; In Vitro Techniques; Kidney Medulla; Male; Microsomes; Prostaglandin-Endoperoxide Synthases; Prostaglandins E; Prostaglandins F; Rats; Time Factors