Urinary Prostanoid Excretion Research Articles

Camelina sativa Oil, Fatty Fish, and Lean Fish Do Not Markedly Affect Urinary Prostanoids in Subjects with Impaired Glucose Metabolism.

Dietary fatty acids are suggested to affect oxidative stress; however, results from interventions have been inconclusive. The aim was to examine if fatty fish, lean fish, and Camelina sativa oil (CSO) affect the urinary prostanoid levels in subjects with impaired glucose metabolism. Altogether 79 participants aged 43-72 years completed a randomized controlled study lasting 12 weeks. There were four parallel groups, fatty fish, lean fish (four fish meals/week in both), CSO providing 10 g/day alpha-linolenic acid (ALA), and control diet with limited fish and ALA containing oil consumption. Urinary prostanoids (prostaglandin F2α , 5-F2t -isoprostanes and 15-F2t -isoprostane metabolites, isofuran, 8-F3t -isoprostanes, and 4-(RS)-4-F4t -neuroprostane) of 72 participants (age: mean (±SD) 58.9 ± 6.5 years; body mass index: 29.3 ± 2.5 kg/m2 ) collected over 12-h were measured using liquid chromatography tandem-mass spectrometry. Plasma phospholipid fatty acids were determined using gas chromatography. Our study showed that the proportion of ALA in plasma phospholipids increased in the CSO group (overall difference among the groups p-value <0.001). In the fatty fish group, proportions of eicosapentaenoic and docosahexaenoic acids increased (overall p-value <0.001 for both). Prostaglandin F2α was higher in the CSO group than in the control group (p < 0.05), however, there were no other significant changes in urinary excretion of other prostanoids among the study groups. At baseline, arachidonic acid in plasma phospholipids was positively (r = 0.247, p < 0.05) and ALA negatively (r = -0.326, p < 0.05) associated with urinary total isoprostanes. In conclusion, CSO, fatty fish, and lean fish consumption do not cause major changes in oxidative stress markers in subjects with impaired glucose tolerance.

Renal cyclooxygenase-2 in obese Zucker (fatty) rats

Cyclooxygenase (COX) isoforms, COX-1 and COX-2, are involved in production of prostanoids in the kidney. Increases in renal COX-2 expression have been implicated in the pathophysiology of progressive renal injury, including type 1 diabetes. Thromboxane A(2) (TxA(2)) has been suggested as the key mediator of these effects resulting in up-regulation of prosclerotic cytokines and extracellular matrix proteins. Unlike type 1 diabetes, renal COX has not been studied in models of type 2 diabetes. Renal cortical COX protein expression, and urinary excretion of stable metabolites of prostaglandin E(2) (PGE(2)) and TxA(2), in association with metabolic parameters, were determined in 4-and 12-week-old Zucker fatty rats (fa/fa rat) (ZDF4 and ZDF12), a model of type 2 diabetes, and in age-matched littermates with no metabolic defect (Zucker lean) (ZL4 and ZL12). Western blotting revealed increased COX-2 expression in ZDF4 as compared to ZL4 (245 +/- 130%) (P < 0.05). This increase in COX-2 was even more apparent in 12-week-old ZDF rats (650 +/- 120%) (P < 0.01). All groups of rats demonstrated COX-2-positive cells in typical cortical localizations [macula densa, thick ascending loop of Henle (TALH)]. In contrast to COX-2, COX-1 expression was 30% lower in ZDF12. These changes in COX expression were associated with enhanced urinary excretion of prostanoids, in parallel with the development of metabolic abnormalities. Moreover, increases in prostanoid excretion in ZDF12 were in part reduced by wortmannin (100 mug/kg), used as inhibitor of insulin signaling. Renal cortical COX-2 protein expression and function were increased in ZDF rats, as compared to controls, whereas COX-1 exhibited opposite regulation. The changes in COX-2 paralleled metabolic abnormalities, and were at least in part a four consequence of hyperinsulinemia. These abnormalities may play a role in renal pathophysiology in this model of type 2 diabetes.

Effect of rofecoxib, etoricoxib, celecoxib, and naproxen on urinary excretion of prostanoids in elderly volunteers

Purpose COX-2 inhibitors (COX2i) and nonselective NSAIDs affect systemic and renal prostaglandin synthesis and may have differential effects on vasoactive eicosanoids [prostacyclin, PGI2; thromboxane, TxB]. This study evaluated the effects of placebo (P), an NSAID [naproxen (N) 500 mg BID], and 3 COX2i [rofecoxib (R) 25 mg QD, etoricoxib (E) 90 mg QD, and celecoxib (C) 200 mg BID] on urinary prostanoids, 11-dehydro TxB2 (TxB-M; systemic TxB production measure), and 2,3 dinor 6-keto PGF1α, (PGI-M; systemic PGI2 production measure). Methods 152 patients (ages 60 to 85 yr) in 2 randomized, double-blind, placebo-controlled, 2-week parallel trials had prostanoids assayed from 8-hr urinary collections at pretreatment and Day 15. Results Effects were consistent for C, N, and P in both studies, so data for the 3 groups were pooled across trials. Results are below: (See Table) Conclusions COX-2 inhibitors had similar but partial reductions (p<0.89) in PGI2 synthesis [significantly less than that caused by naproxen (p<0.05)]. COX-2 inhibitors had no meaningful effect on systemic thromboxane [naproxen caused a substantial reduction (p<0.05) consistent with its effects on ex vivo serum TXB2 production and platelet aggregation]. Clinical Pharmacology & Therapeutics (2004) 75, P34–P34; doi: 10.1016/j.clpt.2003.11.127 Table 1. % Change from baseline in Urinary Excretion of Prostanoids (Mean SE) Treatment N PGI-M N TxB-M Rofecoxib 17 −58.9±4.6 17 −16.9±8.0 Etoricoxib 20 −58.3±4.4 21 0.9±8.9 Celecoxib 38 −58.2±2.9 38 −3.7±5.8 Naproxen 38 −75.1±1.7 38 −84.5±0.9 Placebo 37 −9.1±6.5 38 7.2±6.5

Herbal Medicine.

Herbal Medicine.

Effect of the ingestion of Ginkgo biloba extract on platelet aggregation and urinary prostanoid excretion in healthy and Type 2 diabetic subjects

Enhanced platelet function, particularly in response to collagen, is a common occurrence in diabetes that increases the risk of cardiovascular disease. Ginkgo biloba extract is ingested primarily to improve mental focus but it possesses a blood-thinning potential, which has not been well characterized. This study was designed to compare the effect of ingesting G. biloba extract on platelet aggregation in platelet-rich plasma (PRP) and prostanoid urinary excretion in healthy volunteers and subjects with Type 2 diabetes mellitus (T2DM). Before and after ingesting 120 mg of standardized G. biloba extract for 3 months, platelet aggregation was studied in PRP and urinary metabolites of thromboxane B 2 (TXB 2) and prostacyclin (PGI 2) were measured. In healthy volunteers (age, 42±11 years; BMI, 28.4±4.8 kg/m 2; n=28), the ingestion of G. biloba extract significantly increased fasting insulin and C-peptide (10±4 vs. 12±6 μU/ml, p<0.007 and 1.3±0.8 vs. 2.1±1.1 ng/ml, p<0.001, respectively) and significantly reduced collagen but not PAF-mediated platelet aggregation, converting 21 of 28 subjects with [COL+/EPI+] platelets to the [COL−/EPI+] phenotype. This was accompanied by a reduction of 11-dehydro-TXB 2 from 12.4±6.1 to 10.3±6.1 ng/mg Cr ( p<0.04) and PGI 2 metabolites (2,3-dinor-6-keto-PGF 1α and 6-keto-PGF 1α) from 2.2±0.8 to 1.8±0.8 ng/mg Cr ( p<0.05). In the T2DM subjects (age, 54±8; BMI, 36.6±7.9 kg/m 2; n=19), G. biloba ingestion did not affect pancreatic β-cell function but significantly reduced platelet aggregation, converting 16 of 19 [COL+/EPI+] platelets to the [COL−/EPI+] phenotype. Unlike the healthy volunteers, this was not accompanied by a reduced urinary prostanoid excretion. G. biloba-induced reduction of both classes of prostanoid metabolites in healthy volunteers, but not in T2DM subjects, may suggest a nonselective inhibition of COX-1-mediated TXA 2 in platelets and COX-2-mediated PGI 2 production by the endothelial cells and perhaps platelet-enriched levels of arachidonic acid or COX-1 activity, or both, in T2DM subjects.

Inhibition of cyclooxygenase-2 attenuates urinary prostanoid excretion without affecting renal renin expression.

This study aimed to assess the impact of cyclooxygenase-2 (COX-2) on the secretion and expression of renin in the kidney cortex. For this purpose renocortical COX-2 expression was moderately stimulated by a low-salt diet or strongly stimulated (increase in mRNA about fivefold) by the combination of a low-salt diet and the angiotensin-I-converting enzyme inhibitor ramipril in male Sprague-Dawley rats. None of these manoeuvres changed medullary COX-2 expression or cortical or medullary COX-1 expression. Treatment with low salt plus ramipril but not with low salt alone led to a three- to fourfold increase of the urinary output of all major prostanoids. The selective COX-2 inhibitor rofecoxib (10 mg/kg per day) markedly lowered basal urinary prostanoid excretion and blunted the stimulation of prostanoid excretion during treatment with low salt plus ramipril. The stimulation of renin secretion by the low-salt diet but not by low salt plus ramipril was attenuated by rofecoxib. The low-salt diet led to a moderate increase of renin gene expression, and additional treatment with ramipril caused a 15-fold increase of renin mRNA. However, no effect of rofecoxib on renin gene expression was observed in any group. These findings suggest that stimulation of COX-2 in the renal cortex leads to the increased formation of all major prostanoids. COX-2-derived prostanoids may play a role in the regulation of renin secretion but not in renin gene expression during the intake of a low-salt diet. However, no major relevance of COX-2-derived prostanoids to renin secretion or renin gene expression during ramipril treatment or a combination of ramipril and a low-salt diet was found.

Effects of alcohol and the evening meal on shear-induced platelet aggregation and urinary excretion of prostanoids.

Moderate regular alcohol intake has been found to be associated with a decreased risk for coronary heart disease and stroke. We investigated the effects of acute intake of red wine (60 g ethanol) and a standard dinner under controlled conditions on haemostatic factors. Shear-induced platelet aggregation (SIPA) decreased after the intake of alcohol irrespective of whether the subjects were fasting or not, and also after the intake of food. The intake of alcohol inhibited the postprandial increase of von Willebrand factor multimers. Plasma levels of plasminogen activator inhibitor 1 activity (PAI-1) and serum triglycerides were increased by alcohol. Excretion of the platelet thromboxane A(2) metabolites 11-dehydrothromboxane B(2) and 2,3-dinorthromboxane B(2), as well as the endothelial prostacyclin metabolite 2, 3-dinor-6-ketoprostaglandin F(1)alpha, into urine was not influenced by either alcohol or food. We conclude that eating a dinner together with red wine has no untoward effect on SIPA and that the decrease of SIPA is not specific for alcohol.

Cyclooxygenases 1 and 2 and thromboxane synthase in kidneys of Lyon hypertensive rats

Compared with their two normotensive (LN and LL) controls, genetically hypertensive rats of the Lyon strain (LH) exhibit increased renal vascular resistance and a blunted pressure natriuresis function as well as an increased urinary excretion of vasoconstrictor prostanoids. The aim of this study was to assess in the kidneys of these animals the synthesis of vasoconstrictor or sodium-retaining prostanoids. The relative abundance of the mRNAs of cyclooxygenases (COX) 1 and 2 and of thromboxane A 2 synthase (TXS), was measured by reverse-transcription polymerase chain reaction (RT-PCR) in renal cortex and medulla dissected in groups of male LH, LN, and LL rats either in baseline conditions or after 1 week of salt loading (1.5% NaCl in the drinking water). In basal conditions, at 3 and 11 weeks of age COX1 was expressed in the kidneys of all rats more markedly in medulla than in cortex. COX2 was poorly expressed in the whole kidney. TXS expression was usually too low to be quantified. No difference could be observed among LH, LN, and LL rats. After salt loading, the expression of COX1 was enhanced in the medulla and that of COX2 reduced in the cortex. LH rats differed from controls by a significantly more marked increase in medullary COX1 expression. The present work excludes any primary generalized increase in the renal expression of the genes that control the synthesis of vasoconstrictor prostanoids in LH rats, but suggests that medullary COX1 is upregulated by salt in these animals.

Renal synthesis of prostacyclin and thromboxane in the healthy women: differential effects of a short-term saline loading

It is accepted that the urinary excretions of the stable metabolites of prostaglandin (PG)I2and thromboxane(Tx) A2, 6-keto-PGF1α(6KPGF) and TxB2respectively, provide an accurate estimate of both basal and stimulated renal synthesis of their precursors. The excretory profile of these metabolites has been evaluated in healthy women submitted to a short-term expansion in extracellular fluid volume. Salt retention (SR group,n =6) was induced by physiological saline (0.9% NaCI) i.v. infusions (2 L per day) over a period of 2 days. On the third day the increase in body weight was 0.92 ± 0.27 kg (P⪡0.05). The results of the study have been compared to those previously obtained in normal balance of sodium and potassium (N group, n=20) and in induced salt depletion (SD group, n=14). A common study protocol was used. Basal values of plasma renin activity (PRA) and urinary aldosterone excretion were determined. Renal functional exploration [clearance (cl.) method] was performed during hypotonic polyuria (induced by oral water load) and subsequent moderate antidiuresis (induced by low-dose infusion of an antidiuretic hormone analogue). Urinary 6KPGF and TxB2concentrations were estimated by RIA method and their urinary excretions were determined at both high and low urinary flow rates. The linear regressions of the urinary metabolite excretions vs. urinary flow rate were estimated by using the data obtained in both hypotonic polyuria and antidiuresis. Salt retention (SR vs. N group) was effective in decreasing the basal values of plasma renin activity and urinary aldosterone excretion. Moreover, during hypotonic polyuria it was effective in increasing the absolute and fractional excretions of sodium and chloride, in the absence of significant variations in mean arterial pressure and creatinine cl. Regarding urinary prostanoid excretions the following results were obtained.In conclusion, functionally effective salt retention in healthy women induces a selective stimulation of renal synthesis of prostacyclin, unlike salt depletion, in which the synthesis of both PGI2and TxA2is upregulated.

Renal production of thromboxane and prostaglandins in a rat model of type 2 diabetes

In an investigation of the involvement of prostanoids in the pathogenesis of nephropathy in type 2 diabetes, we repeatedly measured the urinary excretion of prostanoids in both diabetic and healthy rats as the rats aged. Seven rats of the Otsuka Long-Evans Tokushima Fatty strain were used as rats with a model of type 2 diabetes and seven rats of the Long-Evans Tokushima Otsuka strain were used as rats without diabetes. Thromboxane (TX) B2 and 6-keto-prostaglandin (PG) F1α, the amounts of which reflect renal production of TXA2 and PGI2, respectively, and PGE2 in urine collected in metabolic cages were assayed when rats were 14, 30, 46, and 54 weeks old. Plasma glucose and urinary protein excretion also were measured periodically. The mean plasma glucose concentration of the diabetic rats was higher than that of the healthy rats throughout the study. At 30 weeks and later, urinary protein excretion by the diabetic rats was greater than that of the healthy rats, and it increased with age. Urinary excretion of TXB2 by the diabetic rats was higher than that of the healthy rats at 14 weeks (52.4 ± 23.5 vs. 27.0 ± 2.6 ng/day; mean ± SD, P = .015) and the difference continued to the end of the experiment. Urinary excretion of 6-keto-PGF1α by the diabetic rats was high at 14 weeks (52.3 ± 12.8 vs. 26.9 ± 4.6 ng/day; mean ± SD, P < .001) but decreased with age and was the same as that of the healthy rats at 54 weeks. The urinary excretion of PGE2 by the two groups of rats was not significantly different. These results suggest that altered renal production of TXA2 and PGI2 is involved in the pathogenesis of diabetic nephropathy in rats with type 2 diabetes.

Acetaminophen inhibits spinal prostaglandin E2 release after peripheral noxious stimulation.

Prostaglandin play a pivotal role in spinal nociceptive processing. At therapeutic concentrations, acetaminophen is not a cyclooxygenase inhibitor. inhibitor. Thus, it is antinociceptive without having antiinflammatory or gastrointestinal toxic effects. This study evaluated the role of spinal prostaglandin E2 (PGE2) in antinociception produced by intraperitoneally administered acetaminophen. The PGE2 concentrations in the dorsal horn of the spinal cord were measured after formalin was injected into the hind paw of rats. The effect of antinociceptive doses of acetaminophen (100, 200, and 300 mg/kg given intraperitoneally) on PGE2 levels and flinching behavior was monitored Spinal PGE2 and acetaminophen concentrations were obtained by microdialysis using a probe that was implanted transversely through the dorsal horn of the spinal cord at L4. Furthermore, the effects of acetaminophen on urinary prostaglandin excretion were determined. Intraperitoneal administration of acetaminophen resulted in a significant decrease in spinal PGE2 release that was associated with a significant reduction in the flinching behavior in the formalin test Acetaminophen was distributed rapidly into the spinal cord with maximum dialysate concentrations 4560 min after intraperitoneal administration. Urinary excretion of prostanoids (PGE2, PGF2alpha, and 6-keto-PGF1alpha) was not significantly altered after acetaminophen administration. The data confirm the importance of PGE2 in spinal nociceptive processing. The results suggest that antinociception after acetaminophen administration is mediated, at least in part, by inhibition of spinal PGE2 release. The mechanism, however, remains unknown. The finding that urinary excretion of prostaglandins was not affected might explain why acetaminophen is antinociceptive but does not compromise renal safety.

Renal function and urinary prostanoid excretions in salt-depleted women: comparative effects of enalapril and indomethacin treatments

The acute effects on urinary prostanoid excretion and on renal function induced by pharmacological inhibition of either the angiotensin-converting enzyme or of the cyclooxygenase system, respectively, have been studied in healthy salt-depleted women. Two experimental groups were studied during salt depletion, SD1 (n=8) and SD2 (n=6). Salt depletion was obtained by combining a low sodium chloride dietary intake (≦60 mmol per day) with natriuretic and potassium sparing treatment. Paired studies were performed in the absence and in the presence of enalapril (SD1 group) or indomethacin (SD2 group). In both paired studies renal function was estimated by the clearance (cl.) method and the urinary concentrations of PGE2, 6-keto-PGF1αand TXB2were estimated by RIA during sustained hypotonic polyuria (induced by oral water load). Enalapril did not influence urinary excretion of prostanoids. Its main significant effects were: (a) a reduction in mean arterial pressure (MAP); (b) an increase in free-water cl. (CH20) and a reduction in osmolar cl. (Cosm); (c) a reduction in the absolute and fractional urinary excretions of sodium and chloride; and (d) a reduction in both the plasma concentration and urinary excretion of potassium. The urinary flow rate and the creatinine cl. were not significantly affected. Indomethacin reduced urinary excretion of prostanoids and in addition it produced the following significant effects: (a) a reduction in urinary flow rate, CH20and Cosmvalues, and in absolute and fractional urinary excretions of sodium and chloride; and (b) an increase in plasma potassium concentration. MAP, creatinine cl. and urinary potassium excretion were not significantly affected. With regard to the main parameters, both enalapril and indomethacin exerted similar effects on urinary sodium and chloride excretion but opposite effects on CH20and plasma potassium concentration.In conclusion, after enalapril in a salt-depleted state, the functional expression of acute angiotensin II deprivation was partially masked by the activation of a homeostatic system responsible both for improvement in renal salt conservation and for facilitated cellular potassium uptake. After indomethacin in the same setting, the results were consistent with a differential role of prostanoids in modulating or mediating the activities of neuro-hormonal agonists.

Effects of experimental salt depletion on urinary prostanoid excretions in normal women

The effects of moderate salt depletion on urinary excretions of prostanoids (PG)E 2, 6-keto-PGF 1α (6KPGF) and thromboxane (TX)B 2 have been investigated in healthy women (SD group, n = 14). Salt depletion was obtained by combining a low sodium chloride dietary intake (≤ 60 mmol per day) with natriuretic and potassium sparing treatment. At the end of the treatment, the cumulative sodium deficit was 438 ± 42 mmol (mean ± SEM). Plasma renin activity (PRA) and urinary aldosterone excretion were determined in basal conditions. Renal functional exploration was performed during hypotonic polyuria (by oral water load) and subsequent moderate antidiuresis (by low dose infusion of an antidiuretic hormone analogue). In both phases, renal function was estimated by the clearance (cl.) method and the urinary concentrations of PGE 2, 6KPGF and TXB 2 by RIA method. The control group was composed of 20 healthy women in normal sodium and potassium balance (N group). Salt depletion was effective in increasing the basal values of plasma renin activity (PRA) and urinary aldosterone excretion. Moreover, it was effective in inducing the following during polyuria: (a) a depression of the diuretic response to water load in presence of a reduction in plasma osmolality; (b) a reduction in creatinine cl. in the absence of significant changes in mean arterial pressure; (c) an increase in the fractional reabsorption of sodium and chloride, in particular at the level of the diluting segments. Both in polyuria and in antidiuresis, the excretions of 6KPGF and TXB 2 were higher in the SD vs. N group, while the excretion of PGE 2 was not significantly different. In SD and N pooled groups, significant positive correlations were shown between basal PRA and urinary excretions during polyuria of 6KGPF and TXB 2, (but not of PGE 2) as well as between the excretions of the two metabolites. In conclusion, functionally effective salt depletion induces in healthy women a stimulation of renal synthesis of both prostacyclin and thromboxane. The excretory data do not give evidence of a similar effect on PGE 2 synthesis.

Prostanoid Formation during Feeding of a Preterm Formula with Long-Chain Polyunsaturated Fatty Acids in Healthy Preterm Infants during the First Weeks of Life

The objective of this study was to evaluate the effect of conventional and long-chain polyunsaturated fatty acids (LCP)-enriched preterm formula on prostanoid formation in preterm infants during their first weeks of life. In a prospective, randomized, double-blind study, healthy infants received either formula enriched with LCP (n = 10), standard preterm formula (n = 10), or (expressed) breast milk (n = 10). Urine was sampled, and anthropometric measurements were taken at study entry and after the study period of 3 wk. In vivo formation of prostaglandin E2, thromboxane A2, and prostacyclin was evaluated by measuring the urinary excretion of the respective index metabolities by gas chromatography-mass spectrometry. There were no significant differences in urinary prostanoid excretion and anthropometric data between the groups at the end of the study period. We conclude that neither conventional formula nor supplementation of a preterm formula with LCP for a period of 3 wk substantially influence prostanoid formation in healthy preterm infants.

Measurements of Urinary Prostaglandins in Young Ovulatory Women During the Menstrual Cycle and in Postmenopausal Women

The purpose of the present work was to study the prostaglandin excretion in young nonpregnant ovulatory women during the menstrual cycle on the one hand and in postmenopausal women on the other hand and to investigate the influence of female sex hormones (estradiol, progesterone) on urinary prostanoid excretion. Urinary excretion rates of prostaglandin E 2 (PGE 2), 6-keto-PGF 1α, thromboxane B 2 (TxB 2) and their metabolites PGE-M (11α-hydroxy-9,15-dioxo-2,3,4,5,20-pentanor-19-carboxyprostanoic acid), 2,3-dinor-6-keto-PGF 1α, 2,3-dinor-TxB 2 and 11-dehydro-TxB 2 were determined by gas chromatography-triple stage quadrupole mass spectrometry (GC/MS/MS) in 41 young nonpregnant women during the follicular phase and during the luteal phase and in 23 postmenopausal women. Excretion rates of all urinary prostanoids were not significantly different in the follicular phase when compared with the luteal phase. In contrast to the young ovulatory women, PGE 2 and TxB 2 were significantly higher in postmenopausal women. Concerning the other prostaglandins significant differences between these groups of women did not exist. Although serum levels of estradiol and progesterone were different in young and postmenopausal women, sex hormones have not been shown to correlate with prostaglandins. Our data do not suggest sex hormones to be responsible for the difference in the prostaglandin excretion in women of reproductive age and in women in the menopause. Further systematic investigations into age dependency of prostaglandin excretion in women are necessary.

Altered levels of urinary prostanoids in lead-exposed workers

This paper describes the alteration of the urinary excretion of prostanoids in workers occupationally exposed to lead. For this purpose, the following groups were studied: Group 1 ( n = 62): controls; Group 2 ( n = 29): risk group; and Group 3 ( n = 69): exposed group. Urine samples were collected for prostanoid analysis and lead blood levels were analyzed. Our results demonstrate that urinary excretion of prostanoids is already altered even at levels of lead in blood = 200 μg/l. Owing to their sensitivity, urinary prostanoids could be useful markers of early renal changes associated with lead exposure. However, underlying mechanisms should be elucidated and the health significance of such changes should be assessed before any conclusion is drawn.

Interactions between the renin-angiotensin system and prostanoids in modulating renal function in potassium-depleted healthy women

Plasma renin activity (PRA) and urinary aldosterone excretion were determined in healthy women with normal potassium balance (N, n = 20) or experimental potassium depletion (KD). KD was induced by natriuretic treatment — associated with replacement of net NaCl and water losses — and low dietary potassium intake (≤ 10 mmol/d). By using different depletion patterns, three groups were obtained with cumulative potassium deficits (mean ± SEM) of 160 ± 43 (KD1, n = 8), 198 ± 22 (KD2, n = 6) and 215 ± 54 mmol (KD3, n = 6). The renal function by the clearance (cl.) method and urinary concentrations of prostaglandin E 2 (PGE 2), 6-keto-PGF 1α (6KPGF), and thromboxane B 2 (TXB 2) by the RIA method were estimated during hypotonic polyuria (oral water load) and subsequent moderate antidiuresis induced by low-dose infusion of lysine-8-vasopressin (LVP). 1. 1. In all KD groups the depletion treatment significantly reduced both potassium plasma concentration (P K) and urinary potassium excretion while it increased basal PRA; the basal urinary aldosterone excretion was not significantly different from normokalemic controls. In the KD3 vs KD1 group the P κ value was significantly lower. 2. 2. In both KD2 and KD3 groups as compared to the N group, several hypokalemic-like renal dysfunctions — absent in the KD1 group — occurred. Particularly, in the KD2 + KD3 vs N group the renal ability in both urine diluting (water load) and concentrating (LVP infusion) was significantly impaired. 3. 3. In the KD2 vs N group during polyuria the urinary excretions of the three prostanoids were significantly lower, while in the KD3 vs N group only that of PGE 2 was significantly lower. During LVP infusion in both KD2 and KD3 vs N group the differences in urinary prostanoid excretions were attenuated. The data suggest that a pathophysiologically critical degree of KD depressed the dynamic response of renal prostanoid synthesis to polyuria. However, in connection with and probably because of higher values of PRA, the hyporeactivity to polyuria of the renal synthesis of 6KPGF and TXB 2 precursors was corrected.

Systemic and Uteroplacental Hemodynamics and the Prostaglandin System in Pregnancy-Induced Hypertension and Normal Pregnancy

Objective: The aim of this prospective study was to establish whether or not there is any relationship between activation of the prostaglandin system and changes in systemic and uteroplacental hemodynamics in pregnancy.Methods: Urinary excretion of prostaglandin E2 (PGE2) and the main metabolites of prostacyclin (PGI2) and thromboxane A2 (TXA2) was determined, and indices of the vascular resistance of the uteroplacental bed were measured in 10 normotensive women studied in each trimester of pregnancy and in 15 women with pregnancy-induced hypertension in the third trimester. None of these subjects presented renal insufficiency or coagulation disorders, and all were monitored up to delivery to assess the outcome of pregnancy. Urinary excretion of prostanoids was measured by radioimmunoassay after purification of samples with high-pressure liquid chromatography. Blood pressure was measured and vascular resistance indices were calculated, using ultrasonography to measure the amplitude of systolic and diastol...

Dietary supplementation with primrose oil or fish oil does not change urinary excretion of prostacyclin and thromboxane metabolites in pre-eclamptic women

To study whether balance between antiaggregatory, vasodilatory prostacyclin (PGI 2) and proaggregatory, vasoconstrictory thromboxane A 2 (TXA 2) could be affected by dietary manipulation, 18 pre-eclamptic women were treated in randomized order between 31 and 36 weeks of gestation either with primrose oil (n =7), with fish oil (n =5), or with placebo (n = 6). Urinary excretions of the degradation products of PGI 2 (6-keto-PGF 1α, 2,3-dinor-6-keto-PGF 1α) and TXA 2 (TXB 2, 2,3-dinor-TXB 2) were measured in 24 h urines before and serially during the supplementation. Fatty acid supplementation did not affect urinary prostanoid excretions or clinical signs of pre-eclampsia.

Role of atrial natriuretic peptide in the pathogenesis of sodium retention in IDDM with and without glomerular hyperfiltration.

The pathogenetic determinants of sodium retention in IDDM are not fully understood. The aim of this study was to elucidate the action of ANP in 11 IDDM patients with high GFR (greater than or equal to 135 ml.min-1 x 1.73 m-2), referred to here as HF patients; in 10 IDDM patients with normal GFR (greater than 90 and less than 135 ml.min-1 x 1.73 m-2), referred to here as NF patients; and 12 control subjects, here called C subjects, at baseline and during saline infusion administered on the basis of either body weight (2 mmol.kg-1 x 60 min-1; Saline 1) or of ECV (12 mM.ECVL-1 x 90 min-1; Saline 2) during euglycemic insulin-glucose clamp. C subjects and both HF and NF IDDM patients received a second Saline 1 infusion accompanied by ANP infusion (0.02 microgram.kg-1.min-1) at euglycemic levels. HF and NF patients were studied again after 3 mo of treatment with (10 mg/day). Quinapril (CI 906, Malesci, Florence, Italy), an ACE inhibitor without sulfhydryl group. At baseline, both HF and NF IDDM patients had higher plasma ANP concentrations than C subjects (HF, 36 +/- 4, P less than 0.01 and NF, 34 +/- 3, P less than 0.01 vs. C, 19 +/- 3 pg/ml). Plasma ANP and natriuretic response to isotonic volume expansion was impaired both in HF (44 +/- 8 pg/ml, NS vs. base) and NF (40 +/- 7 pg/ml, NS vs. base) compared with C (41 +/- 4 pg/ml, P less than 0.01 vs. base) during Saline 1. On the contrary, plasma ANP response to Saline 2 was similar in HF and NF patients and C subjects, but IDDM patients had still lower urinary sodium excretion rates. The simultaneous administration of ANP and Saline 1 resulted in comparable plasma ANP plateaus in C subjects and HF and NF patients. However, urinary sodium excretion rate was significantly lower in HF and NF patients than in C subjects: HF, 267 +/- 64, P less than 0.01 and NF, 281 +/- 42, P less than 0.01 vs. C, 424 +/- 39 mumol.min-1 x 1.73 m-2. During simultaneous administration of ANP and Saline 1, GFR and FF increased in C subjects, but not in HF and NF patients. HF and NF patients had higher urinary vasodilatory prostanoid excretion rates than C subjects at baseline. Saline infusion did not change urinary excretion rate of prostanoids either in C subjects or IDDM patients (both NF and HF).(ABSTRACT TRUNCATED AT 400 WORDS)