thromboxane-b2 and Potassium-Deficiency

Plasma renin activity (PRA), urinary excretions of PGE2, 6-keto-PGF1 alpha (6KPGF), TXB2 and renal function were determined in healthy women both in normal potassium balance (N, n = 14) and in experimental potassium depletion (KD). KD was induced by natriuretic treatment--associated to replacement of net NaCl and water losses--in the presence of either normal (congruent to 50 mmol/d) or low (less than or equal to 10 mmol/d) dietary potassium intake. By using different depletive patterns, three groups with estimated cumulative potassium deficit (mean +/- SEM) of 124 +/- 38 (KD0, n = 8), 160 +/- 43 (KD1, n = 8) and 198 +/- 22 mmol (KD2, n = 6), respectively, were obtained. Renal function by the clearance (cl.) method and urinary prostanoid concentrations by the RIA method were estimated during hypotonic polyuria (oral water load) and subsequent moderate antidiuresis induced by a low-dose infusion of lysine-8-vasopressin. 1. In KD0 group the potassium depletive treatment was inefficacious in significantly reducing either the plasma potassium concentration (PK) or the urinary potassium excretion (UKV). The reductions of PK and UKV as well as the enhancement of PRA became significant in KD1 and KD2 groups. 2. The urinary prostanoid excretions were not significantly changed in the KD0 and KD1 groups while in the KD2 group they were reduced, mainly concerning the urinary 6KPGF excretion. 3. Furthermore in the KD2 group, with larger potassium depletion, some of the typical hypokalemic renal dysfunctions appeared. The data suggest that a pathophysiologically critical degree of potassium depletion is associated with an inhibited renal prostanoid synthesis as well as an increased renin secretion.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Chlorides; Dinoprostone; Female; Glomerular Filtration Rate; Humans; Indomethacin; Kidney Function Tests; Natriuresis; Polyuria; Potassium; Potassium Deficiency; Renin; Thromboxane B2; Water Intoxication

Renal function has been studied by the clearance (cl.) method during hypotonic polyuria--four 15-min cl. periods--and successive antidiuresis--two 60-min cl. periods (A1, A2)--induced by lysine-8-vasopressin (LVP), 5 mU in bolus followed by infusion at a rate of 0.04 mU/min. The endogenous creatinine cl. (Cc) and the osmotic cls. (Cosm, CH2O) were determined by the usual methods as well as the absolute and fractional urinary excretions of water, sodium, chloride and potassium. The urinary concentrations of PGE2, 6-keto-PGF1 alpha and TxB2 were determined by the RIA method. This study protocol has been applied to 28 healthy women either in normal potassium balance (N, n = 14) or after potassium depletion (KD) induced by low potassium dietary intake (less than or equal to 10 meq/d) plus natriuretic treatment according to two different time patterns: two KD groups were obtained with potassium cumulative deficit of 160 +/- 43 (D2, n = 8) and 198 +/- 22 meq (D3, n = 6). The early % effects of LVP, i.e. (A1-P)% of P (mean polyuria), were significantly different only in D3 as compared to N. Precisely, the LVP-effect to reduce Cc was blunted; moreover a LVP-effect to reduce renal sodium and chloride fractional excretions and a tendentiously enhanced LVP-effect to reduce water fractional excretion were observed. These tubular effects are likely related to the inhibited renal synthesis of prostanoids in the D3 group.

Topics: 6-Ketoprostaglandin F1 alpha; Dinoprostone; Female; Humans; Kidney; Lypressin; Polyuria; Potassium Deficiency; Thromboxane B2

Renal function has been studied by the clearance (cl.) method during hypotonic polyuria--four 15-min cl. periods--and successive antidiuresis--two 60-min cl. periods (A1, A2)--induced by lysine-8-vasopressin (LVP), 5 mU in bolus followed by infusion at a rate of 0.04 mU/min. The endogenous creatinine cl. (Cc) and the osmotic cls. (Cosm, CH2O) were determined by the usual methods as well as the absolute and fractional urinary excretions of water, sodium, chloride and potassium. The urinary concentrations of PGE2, 6-keto-PGF1 alpha and TxB2 were determined by the RIA method. This study protocol has been applied to 20 healthy women submitted to paired functional explorations in both the absence and presence of indomethacin (100 mg i.m.); the drug effects have been evaluated in both normal potassium balance (N2, n = 6) and in two groups of potassium depletion (KD) with potassium cumulative deficit of 160 +/- 43 (D2, n = 8) and 198 +/- 22 meq (D3, n = 6), respectively. As regards the early % effects of LVP, i.e. (A1-P)% of P (mean polyuria), the inhibition of prostanoid synthesis with indomethacin produced significant changes: 1) an enhanced reduction in renal chloride excretion in all experimental groups; 2) a reduction in renal sodium and chloride fractional excretions in both KD groups; 3) an enhanced antidiuretic effect in D3 only, i.e. in the experimental condition with inhibition of prostanoid renal synthesis present during the control study.

Topics: 6-Ketoprostaglandin F1 alpha; Dinoprostone; Female; Humans; Indomethacin; Kidney; Lypressin; Polyuria; Potassium Deficiency; Thromboxane B2

The renal function has been evaluated by clearance (cl.) method during hypotonic polyuria and successive moderate antidiuresis induced by a low dose of lysine-8-vasopressin; four 15 min and two 60 min cl. periods were performed, respectively. Glomerular filtration rate was estimated by creatinine cl.; the osmotic cl. (Cosm, CH2O), the absolute and fractional excretions of water, sodium, potassium and chloride were determined by usual methods. The urinary concentrations of PGE2, 6-keto-PGF1 alpha (6KPGF) and TxB2 were measured by RIA. The study protocol was applied in normal potassium balance and experimental potassium balance (KD), both in absence and presence of indomethacin. In KD groups with a potassium cumulative deficit of 198.4 +/- 22.2 meq (D3; n = 6) during polyuria significant correlations are consistent with the hypothesis that the lower the plasma potassium concentration is the higher the urinary chloride excretion and the inhibition of distal fractional chloride reabsorption. Moreover, by utilizing the polyuria and antidiuresis data pool, the effects of urine flow rate changes on PGE2 and 6KPGF urinary excretions are blunted as compared to normal potassium balance (n = 14). After indomethacin treatment (D3.I) the following functional relationships are disclosed: a) the lower the kaliemia is the lower the urinary chloride and potassium excretions and the higher the fractional isosmotic reabsorption; b) the lower the urinary potassium excretion is the lower the urinary chloride excretion. In both D3 and D3.I experimental groups the positive correlation between urinary chloride excretion and urinary potassium excretion is significant.

Topics: 6-Ketoprostaglandin F1 alpha; Chlorides; Dinoprostone; Diuresis; Humans; Indomethacin; Kidney Function Tests; Kidney Tubules; Kidney Tubules, Distal; Lypressin; Potassium; Potassium Deficiency; Thromboxane B2

We demonstrated that potassium depletion significantly increased gentamicin nephrotoxicity in Sprague-Dawley rats (100 mg X kg-1 X day-1). To determine whether this enhanced toxicity was mediated by renin secretion, we evaluated the effect of a converting enzyme inhibitor in this model. When we administered the combination of captopril (100 mg X kg-1 X day-1) and gentamicin in potassium-depleted rats, we observed a surprising and significant adverse effect of this combination on the clearances of inulin (CIn) and PAH (CPAH) and renal blood flow (RBF). Pretreatment with indomethacin significantly improved CIn and CPAH, and potassium repletion abolished this effect entirely. In potassium-depleted animals that received both gentamicin and captopril, the intra-arterial administration of imidazole, a thromboxane synthetase inhibitor, significantly reduced urinary TXB2 excretion and significantly improved RBF and CIn in vivo. In the same group of animals, administration of the kallikrein antagonist aprotinin also significantly increased both RBF and CIn. To measure total renal thromboxane B2 production (TXB2), we perfused kidneys ex vivo with cell-free perfusate. Three groups of animals were studied: potassium-repleted control animals, potassium-depleted control animals, and potassium-depleted animals treated with gentamicin alone, captopril alone, or the combination of gentamicin and captopril. We measured TXB2 in renal venous effluent by radioimmunoassay. Ex vivo perfused kidneys from potassium-depleted control animals produced significantly more TXB2 than potassium-repleted controls. Kidneys from potassium-depleted animals that received both gentamicin and captopril produced significantly greater amounts of TXB2 than did kidneys from potassium-depleted animals treated with captopril alone, gentamicin alone, or control potassium-depleted kidneys. The administration of imidazole ex vivo at a rate equivalent to in vivo administration (10 microM/min) reduced TXB2 production by potassium-depleted kidneys that received the combination of gentamicin and captopril to that of potassium-repleted control kidneys. These results suggest that the deleterious effect of captopril in potassium-depleted rats that received gentamicin is due at least in part to kinin-stimulated renal TXB2 production.

Topics: Aminoglycosides; Angiotensin-Converting Enzyme Inhibitors; Animals; Aprotinin; Captopril; Gentamicins; Imidazoles; Indomethacin; Inulin; Kidney; Kidney Function Tests; Male; p-Aminohippuric Acid; Potassium Deficiency; Radioimmunoassay; Rats; Rats, Inbred Strains; Renal Circulation; Renin; Thromboxane B2

There is a considerable amount of interest in prostaglandin E2 (PGE2) metabolism in potassium depletion, but the findings remain inconclusive. Thromboxane A2 (TXA2) is another type of prostaglandin with a vasoconstrictive property and its biosynthesis in the kidney is altered under pathophysiological conditions. We investigated the production of both immunoassayable PGE2 and thromboxane B2 (TXB2), a chemically stable metabolite of TXA2, in the chronically K+-depleted rat kidney. During a 90-min in vitro incubation of papillary slices obtained from K+-depleted rats, TXB2 production was increased, but PGE2 biosynthesis was decreased and PGF2 alpha remained unaltered compared with control rats. In the cortex, TXB2 production was low, but it was greater in K+-depleted rats compared with control rats. Deletion of K+ from the incubation medium had no measurable effect on either TXB2 or PGE2 production in both K+-depleted and control rats. Formation of [14C]TXB2 from [14C]PGH2 by microsomes from renal papilla was greater in K+-depleted rats compared with control rats, suggesting that the increased TXB2 production in the K+-depleted rat kidney is probably due to an activation of TXA2 synthetase.

Topics: Animals; Imidazoles; In Vitro Techniques; Indomethacin; Kidney; Male; Microsomes; Potassium; Potassium Deficiency; Prostaglandins; Prostaglandins E; Radioimmunoassay; Rats; Thromboxane B2; Thromboxanes