Prostaglandins kukotrienes and Essential Cl Loneman Grout UK Ltd 1992

Fatty Acids

(1992) 46, 21-26

Urinary Prostanoid Excretion in Healthy Women with Different Degrees of Induced Potassium Depletion G. C. Agnoli, R. Borgatti,

M. Cacciari, E. Ikonomu,

P. Lenzi and M. Marinelli*

Cattedra di Semeiotica Medica, Istituto di Clinica Medica II, Universitir di Bologna, Via Massarenti 9, 40138 Bologna, Italy and *Servizio di Medicina Nucleare USL 27, Bologna, Italy (Reprint requests to GCA) Plasma renin activity (PRA), urinary excretions of PGE2, 6-keto-PGF,, (6KPGF), TXBz 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 (= 50 mmol/d) or low (I 10 mmol/d) dietary potassium intake. By using dilferent depletive patterns, three groups with estimated cumulative potassium deficit (mean f SEM) of 124 f 38 (KDO, n = 8), 160 + 43 (KDl, 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 sub: sequent moderate antidiuresis induced by a low-dose infusion of lysine-8-vasopressin. 1. In KDO group the potassium depletive treatment was inefficacious in significantly reducing either the plasma potassium concentration (Px) or the urinary potassium excretion (UxV). The reductions of Px and UxV as well as the enhancement of PRA became significant in KDl and KD2 groups. 2. The urinary prostanoid excretions were not significantly changed in the KDO and KDl 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.

ABSTRACT.

INTRODUCTION

analogously, that urinary 6KPGF and TXB2 excre-. tions are correlated to the renal synthesis of the respective primary prostanoids (11). Since potassium depletion can affect spontaneous diuresis by different dysfunctions and diuresis itself is an important determinant of the urinary prostanoid excretion (12-16), our study protocol included a hypotonic polyuria (oral water load) and a subsequent antidiuresis obtained by low-dose infusion of lysine-&vasopressin (LVP). The aim of this protocol was to evaluate the urinary prostanoid excretions at different levels of diuresis. Moreover, it allowed us to obtain renal functional data especially as regards the diluting segment function during hypotonic polyuria and the renal response to LVP infusion. Moreover, the effective role of prostanoids in the control of the renal function has been tested by further studies in potassium depletion associated to cyclooxygenase inhibition. Portions of this study have previously been pub-

Some hemodynamic and renal dysfunctions induced by potassium depletion are apparently compatible with an increased prostanoid synthesis (for review see 1). However, the studies performed to assess this hypothesis have provided divergent results depending on the animal species, the potassium depletive method and the chemical species of urinary prostanoid assayed (2-9). The main purpose of the present work was to study the effects of moderate potassium depletions, induced in healthy women, on urinary prostaglandin (PG) EZ, 6-keto-PGFi, (6KPGF) and thromboxane (TX) Bz excretions. It is admitted that urinary PGE2 excretion reflects its renal synthesis (10) and,

Data received 24 September 1991 Data accepted 13 November 1991 21

22

Prostaglandins Leukotrienes

and Essential Fatty Acids

lished (16). In the present paper we provide evidence that the renal prostanoid synthesis is impaired in potassium depletion of moderate degree but adequate to induce the renal dysfunctions typical of hypokalemia.

SUBJECTS AND METHODS Subjects The study was performed

in women aged 38 + 2.3 years (mean f SEM) free from renal, cardiovascular and metabolic diseases, and scheduled so as to avoid the menstrual period. All subjects, hospitalized and informed about the study protocol, gave their consent. The study protocol was in agreement with the Helsinki declaration (4th article) and previously approved by the Independent Review Board of the Faculty of Medicine of Bologna University. Experimental

conditions and potassium

depletive

treatments 28 subjects have been studied in normal potassium

balance and in potassium depletion respectively. In 8 of them paired studies in both conditions (Nl and KDO groups) were performed. All subjects were submitted for 4 days to a normal sodium (- 150 mmol/d) and potassium (- 50 mmol/d) dietary intake. Studies in normal potassium balance In 14 subjects the above-mentioned diet was applied. In 8 of them a single functional exploration (Nl group) was performed; in the remaining 6 subjects paired functional explorations, both in the absence (N2 group) and presence of indomethacin (N2.1), were performed. Studies in potassium depletion Potassium depletion was induced by natriuretic treatment in the presence of a normal or low (5 10 mmol/d) potassium content diet. The daily diuresis, urinary sodium and potassium excretions as well as plasma sodium and potassium concentrations were determined during potassium depletive treatments. The NaCl and HZ0 net losses induced by natriuretic drugs were restored, on a quantitative basis, by saline infusion. The natriuretic treatment was stopped when plasma potassium concentration fell to about 2.5 mmol/l. The potassium cumulative deficit was estimated as cumulative potassium intake minus cumulative urinary potassium excretion over the whole period of potassium depletive treatment. Three experimental groups were obtained. In KDO group (n = 8) the natriuretic treatment by furosemide (Hoechst, Milano, Italy) - 40 mg/d

i.m. for 3 days - was applied in the presence of a normal potassium dietary intake. The body weight variation was -0.25 f 0.16 kg. At the end of depletive treatment the cumulative potassium deficit was 124 f 38 mmol. In the KDl group (n = 8) the low potassium diet was taken for 5 days and the natriuretic treatment by furosemide - 40 mg/d i.m. for 2 or 3 days (i.e. from 2nd to 3rd day or 1st to 3rd day of the diet). During the natriuretic treatment the body weight variation was -0.25 + 0.19 kg. At the end of depletive treatment the cumulative potassium deficit was 160 f 43 mmol. In the KD2 group (n = 6) the low potassium diet was taken for 8 days and the natriuretic treatment with chlorthalidone (Ciba Geigy, Varese, Italy) -50 mg/d p.o. - for 3-4 days (from 4th to 6th day or 3rd to 6th day of the diet). During the natriuretic treatment the body weight variation was -0.92 + 0.40 kg. At the end of depletive treatment the cumulative potassium deficit was 198 + 22 mmol. In the KDO group a single functional exploration was performed while in the KDl and KD2 groups two paired functional explorations in the absence and presence of indomethacin (KD1.1 and KD2.1), respectively, were performed. Either in normal potassium balance or in KD groups the functional exploration in the presence of indomethacin (Chiesi, Parma, Italy) - 100 mg i.m. at the beginning of oral water load - was performed the day after the functional exploration in absence of the drug; during the interval the diet potassium intake was unchanged. The choice of the subjects for the different experimental conditions was random. Basal determinations

and renal functional

exploration

In all experimental groups the basal values of plasma sodium and potassium concentrations and plasma renin activity (PRA) were determined immediately before the oral water load; the urinary aldosterone excretion of the 24 h before was also determined. The hypotonic polyuria was induced by oral water load (20 ml/kg in 60 min) and maintained for 60 min by 5% dextrose solution infusion at a rate equal to half the urinary flow rate reached in order to reduce the retained water load at the beginning of LVP infusion. Four 15-min clearance (cl.) periods were performed; at the end of the second cl. period a blood sample was taken. The reduction of diuresis was obtained by LVP (Sandoz, Basel, CH) Infusion at about half the dose necessary to suppress water diuresis in man (17) in order to blunt the LVP effect on arterial blood pressure. Precisely, in bolo infusion of 5 mU LVP was followed by sustained infusion of 5% dextrose solution containing

Urinary Prostanoid Excretion in Moderate Potassium Depletion

LVP 4 mU/dl at the rate of 1 ml/min for 120 min. Two 60-min cl. periods were performed; at the end of the first cl. period a blood sample was taken. Besides urinary flow rate, V (bladder catheterization), the following parameters on urine and plasma were measured: a) osmolalities (Fiske OMTM osmometer, Uxbridge, MA, USA); b) concentrations (flame sodium and potassium photometer, Corning-EEL 450, Halstead, Essex, UK); c) chloride concentration (chlorimeter, Corning-EEL 920, Halstead, Essex, UK). The glomerular filtration rate was estimated as endogenous creatinine clearance. The electrolyte cls., the osmotic cls. (C,,,, C+,& and the fractional hydro-electrolyte excretions were calculated by standard methods. During hypotonic polyuria the ratios C&&C H~o+CNA and CH,~(CH~O+CCI) where CHlo, the free water cl., C&, and Cc,, the cls. of sodium and chloride respectively - were calculated as an estimation of distal fractional reabsorption of sodium and chloride at the diluting segments (18). Mean arterial pressure (MAP) was calculated by utilizing sphygmomanometer measures. Radioimmunoassay

Urine samples were stored at -20°C immediately after collection. For the radioimmunoassay (RIA) of prostanoids, urines were brought to 4°C and divided into two aliquots. On the first, direct RIA for immunoactive PGE2 levels was performed (19). On the second aliquot, 6KPGF and TXBz RIA was performed after extraction and purification on Bond-Elut SI columns. The prostanoid analytical process and RIA have already been published in detail (16). Commercial RIA kits were used for the PGE*, 6KPGF and TXB2 assays (NEK-020, NEK025, NEK-024, New England Nuclear, Boston, MA, USA) that utilize the iodinate (1251) tracers. The intra- and inter-assay coefficients of variation (n = 10 and n = 6, respectively) were 7.1% and 14% for PGE2, 7.5% and 8% for 6KPGF, 11.4% and 14% for TXB2, respectively. All samples were assayed in duplicate and a standard curve was made for each assay. The accuracy of the assay was assessed by the recovery of standard amounts of PGE2 (S-20 p$ml), 6KPGF (25-100 pg/ml), TXB2 (550 pg/ml) added to pooled urine. The recoveries were 91 + 0.9% for PGE2, 95 -t 0.7% for 6KPGF and 99 -C 5% for TXB2. The detection limit of RIA assays was 1.5 pg/ml for PGE2, 12 pg/ml for 6KPGF and 5 pg/ml for TXB:!. Urinary prostanoid excretions (pg/min) were obtained by multiplying the urinary prostanoid concentrations by the urinary flow rate; the ratios PGE2/I’XB2, 6KPGFnXB2 and PGE2/6KPGF were also calculated. The plasma renin activity (20) and urinary aldo-

sterone concentration methods.

(21) were obtained

23

by RIA

Statistical analysis

Results were expressed as mean + standard error (SEM) values for hypotonic polyuria (P) - calculated from the weighted mean values obtained in each subject during the whole 60-min period as well as for the two cl. periods in presence of LVP (Al, A2). The early and late effects of LVP were estimated in each subject as Al-P and A2-P differences, both absolute and as a % of P; the mean f SEM values of both absolute and % LVP effects were then calculated for each experimental group. Because the mean values of Nl and N2 groups were not significantly different, the N = Nl + N2 group has been utilized for unpaired comparisons with potassium depletion groups. The statistical significance was assessed by analysis of variance (ANOVA) - one-way or two-way where appropriate - and the modified t-test (22). The relationships between different parameters have been evaluated by analysis of simple linear regression. In this paper we shall discuss only the data concerning the P cl. period and the first cl. period during LVP infusion (A cl. period) as well as the earIy % effects of LVP. Moreover, the data regarding the KD2 group are particularly emphasized because they are more suited to the aim of the work. RESULTS In both the KDl and KD2 groups, but not in the KDO one, the following significant differences as compared to the N group, were observed: a) at the end of the depletive treatments the basal values of plasma potassium concentration were lower and the plasma renin activity higher (Table 1); b) during hypotonic polyuria the absolute and fractional urinary excretions of potassium were lower (Table 2). In the KD2 group as compared to the KDl group the cumulative potassium deficit and the indices of potassium depletion were more affected, although not significantly. The basal urinary aldosterone excretion did not differ significantly in the three experimental groups as compared to the N group (Table 1). In the KDO and KDl groups as compared to the N group the urinary prostanoid excretion did not differ in the two cl. periods. However, in the KDl group the 6KPGFpXB2 ratio was significantly lower. In both the KDO and KDl groups, during hypotonic polyuria (Tables 2 & 3), the renal function (except the tubular potassium handling) and the renal response to LVP (unreported data) were not significantly different as compared to the N group.

24

Prostaglandins

Leukotrienes

and Essential

Fatty

Acids

Table 1 Basal data of body weight, plasma concentrations of potassium (Px) and sodium (PNil), plasma renin activity (PRA), urinary aldosterone excretion and potassium cumulative deficit in different conditions of potassium balance Body weight

P,

P,;,

PRA

Urinary Aldo.

kg

mmoi/l

mmol/l

ngimllh

cLp/d

I.1 1.2 3.3 3.9

I3 7 10 8

59.2 60.9 60.4 63.7

N KDO KDI KD2

+ + + f

2.0 2.4 6.6 4.0

4.1 3.7 3.6 3.3

+ f f -c

0.16 0.13 O.l3* 0.11+

142 139 142 142

f + f f

1.1 1.8 1.6 1.5

f 0.1 + 0.4 f 0.8’ z?z0.9

f f + t

K+ Deficit mmol

2.6 2.7 3.5 3.0

Values are mean + SEM obtained before the oral water load. N (n = 14) normal FDO (n = 8). KDI (n = 8) and KD2 (n = 6). experimental groups of potassium p + 0.01, ‘p < 0.001 relative to the N group.

124 f 38 160 + 43 198 _+ 22

potassium depletion.

balance; * p < 0.05.

Table 2 Urinary prostanoids, urinary flow rate, absolute and fractional excretions of potassium different conditions of potassium balance during both hypotonic polyuria (P) and LVP infusion U,V pg/min P

607 f108 239 +38 489 +84 191 f33 718 f164 238 250 313 +100 142* f23

N A P KDO A P KDl A P KD2 A

UIV pg/min

U,V pg/min

U&J,. %

U&J, %

1772 + 210 835 ZlI 104 1852 f 302 663 +60 1287 f 298 511 f 137 510* f 82 193* * 37

975 + 113 505 f 97 1102 * 181 378 + 159 1328 f 321 595 + 134 503’ f 88 270* + 53

73 * 14 58 +9 54 I! 14 76 f 26 I25 f 63 107 + 61 63 f 17 60 f 12

209 * 32 239 + 50 214 f 57 399 + 230 114* f 29 101* f 18 103’ *9 75’ f8

U&J, %

V ml/min

46 28 31 f5 32 f8 28 +s 85 f 32 92 + 40 60 + 13 77’ f9

12.0 + 0.5 5.4 * 0.6 11.3 * 0.6 5.0 + 0.6 11.8 f I.3 5.0 + 0.6 9.0* + 1.2 4.1 f 0.7

U,V, U,V. UrV, urinary excretions of PGE2, 6KPGF and TXB,, respectively; urinary concentration ratios of PGEfiXB z, 6KPGFpXB, and PGEd6KPGF, flow rate; UxV, C&/CE, urinary potassium excretions, absolute and fractional, details see Table 1.

Table 3 Plasma electrolyte concentrations balance during hypotonic polyuria PK mmol/l N KDO KDl KD2

4.0 3.8 3.5 3.0

* f f f

0.1 0.1 0.1* 0.2*

and renal

PC, mmol/l

q. ml/min

95.7 95.5 93.1 88.3

128 143 138 88

f 0.7 f 2.1 f 1.6 f 3.4’

?I + + +

parameters

in different

C “?(I ml/min 6.5 10.2 6.3 4.5+

9.2 8.6 9.7 6.5

+ + + +

uKv

CJC,

pmol/min

%

76.0 + 8.1 39.9 f 4.2 58.0 + 5.8 30. I t 3.5 30.7’ * 10.5 20.3’ + 6.9 16.8* + 3.3 13.8’ + 3.2

14.8 1.2 12.9 * I.5 Il.l+ * I.3 9.1 t I.8 5.9* !I 1.6 6.3’ + 2.1 6.5’ + 1.3 5.7t f I.1 f

U&J .r, U ,/U ,., U& ,, respectively; V. Urinary respectively. For further

conditions

1.04 0.69 0.78 1.62

of potassium

;tl*,:

g&c 0.5 0.6 1.2 l.2*

in (A).

+ + + +

0.10 0.08 0.10 0.26*

87.7 89.9 89.7 79.1

(C”,+C,I)

f f t *

0.97 1.03 1.25 4.87*

Plasma concentrations of potassium and chloride. P, and P,.,, respectively; creatinine clearance, C,; free C,jC L; fractional chloride reabsorption by the water clearance, C&); fractional chloride excretion, diluting segments, C&j(C HIO + C&). For further details see Table 1.

In the KD2 group vs the N group the following differences were observed. 1. The values of urinary 6KPGF and TXB2 excretions, and that of the 6KPGF/TXB2 ratio were significantly lower during both the P and A cl. periods. The urinary PGEz excretion was significantly lower in the A cl. period only. Thus, in this cl. period the urinary prostanoid excretions were lower, in absence of significantly different values of urinary flow rate. significant 2 In the P cl. period the following

functional changes (Tables 2 & 3) were observed: in creatinine cl. in absence of a) a reduction significantly different values of mean arterial pressure (99.7 f 6.8 vs 91.4 k 3 mmHg); in urinary flow rate and CHzo; b) a reduction c) an increase in fractional chloride excretion; in distal fractional chloride d) a reduction reabsorption;

Urinary Prostanoid Excretion in Moderate Potassium Depletion

e) a decrease in plasma chloride concentration. In the KD2 group the indomethacin pretreatment induced a further reduction of the creatinine cl. and the diuretic response to the water load as well as an important decrease in the fractional hydro-electrolyte urinary excretions (unreported data). However, the drug was unable to correct the inhibition of the distal fractional chloride reabsorption (82.1 + 3.1% in KD2.1 vs 79.1 f 4.9% in KD2). 3. In the KD2 group as compared to N group, the LVP was less efficacious in reducing creatinine cl. (-15.9 f 6.9% vs -35.1 + 5.1%, p c 0.05), in absence of significantly different effects on mean arterial pressure (3.9 f 2.2% vs 5.7 f 2.0%). However, the hormone manifested a tendential efficacy in reducing fractional chloride excretion (- 19.4 + 8.2% vs. 8.8 f 8.3%, p < 0.05). The indomethacin pretreatment restored the LVP-induced reduction of the creatinine cl. (-37 f 13.6%). Furthermore, LVP-induced decreases in urinary flow rate (-64 f 9.2% in KD2.1 vs -52 + 8.1% in KD2, p < 0.05) and CHzo (-81 f 12% in KD2.1 vs -68 f 9.2% p < 0.05) were enhanced as well as those in fractional chloride excretion (-41 + 11.7% in KD2.1 vs -19 + 8.2% in KD2, not significant).

DISCUSSION In both the KDl and KD2 groups plasma renin activity was enhanced. Moreover, in the data pool (N, KDO, KDl, KD2 groups) PRA was negatively correlated with plasma potassium concentration (r = -0.516, n = 36, p < O.OOl), in agreement with the observation that potassium depletion stimulates renin secretion (23-25). Probably in our experimental conditions the direct inhibiting effects of hypokalemia on aldosterone secretion (26) were balanced by the opposite ones of the increased levels of circulating angiotensin II. The potassium depletion attained in the KD2 group was efficacious in producing some of the typical hypokalemic renal dysfunctions (for a review, see 1) such as the reduction of glomerular filtration rate, the depressed diuretic response to water load and the inhibition of distal fractional chloride reabsorption. This inhibition appears to be an early expression of the renal chloride wasting induced by severe potassium depletion in man and experimental animals, and probably depends on hypokalemic impairment of the chloride transport in the thick ascending limb of Henle’s loop (27-29). The defect in the distal chloride transport was not corrected by indomethacin according to its dependence on hypokalemia itself.

25

The LVP-induced reduction of the glomerular filtration rate was depressed in the KD2 group as compared to N. This finding is in agreement with the blunted responsiveness of the vessels to the pressor hormones observed in different animal species chronically potassium depleted (2, 4, 7, 30). In potassium depletion of the KD2 group the concurrent depression of vasodilating prostanoid production probably restrained the hypokalemic vascular hyporeactivity. Indeed, further inhibition of prostanoid synthesis (indomethacin) restored the LVP effect on the glomerular filtration rate. In the KD2 group both in polyuria and antidiuresis urinary prostanoid excretions were depressed, suggesting a reduced renal synthesis of these metabolites. Furthermore, 1) the mean values of the urinary prostanoid ratios (Table 2), and 2) the significant direct correlations between plasma potassium concentration and urinary 6KPGF excretion (r = 0.450, n = 36, p < 0.01) as well as urinary 6KPGF/TXB2 ratio (r = 0.413, n = 36, p < O.OS), provide indirect evidence that potassium depletion preferentially inhibited the renal production of prostacyclin, especially compared to thromboxane synthesis. In a variety of pathophysiologic settings in which the vasoconstrictor systems (catecholamines, angiotensin II, vasopressin) are activated, the synthesis of the renal vasodilating prostanoids is stimulated and appears to play a protective role on local hemodynamics (for a review see 31). At variance to this notion, the present results demonstrate that potassium depletion was effective in dissociating the respective behaviours of the renin secretion and the renal prostanoid synthesis, particularly that of PGIz. The inhibition of renal prostanoid synthesis in potassium depletion may provide a protective mechanism as regards the potassium and chloride homeostasis. It is reasonable to infer that the inhibition of the vasodilating prostanoids reduced the background vasodilatory ‘tone’ and enabled angiotensin II to constrict the renal preglomerular vessels (32). Likewise the depressed medullary prostanoids might be a mechanism adequate to improve the tubular responsiveness to antidiuretic hormone, in particular concerning NaCl transport of Henle’s loop (33). This hypothesis is supported by the significant positive correlation in the data of all experimental conditions (N, N1.1, KDO, KDl, KD1.1, KD2, KD2.1) between the % LVP effect on the fractional chloride excretion and urinary PGE2 excretion during hypotonic polyuria (r = 0.446, n = 56, p < 0.001). By an interplay between glomerular and tubular distal effects the renal conservation of potassium might be improved and the urinary chloride dispersion moderated. In conclusion, the results indicate that a moderate potassium depletion, but adequate to induce some of the typical hypokalemic renal dysfunctions, in-

26

Prostaglandins Leukotrienes

hibited renal prostanoid lated renin secretion.

and Essential Fatty Acids

synthesis while it stimu-

Acknowledgment The authors thank Mrs Giuliana Giuliani for secretarial help.

References 1. Raymond K H and Kunau R T jr. Hypokalemic states. pp. 523-525 in Clinical Disorders of Fluid and Electrolyte Metabolism (M H Maxwell, C H Kleeman, R G Norins eds) McGraw-Hill Co., New York, 1987. 2. Galvez 0 G, Bay W H, Roberts B W and Ferris T F. The hemodynamic effects of potassium deficiency in the dog. Circulation Research (Suppl. I) 40: 11-16, 1977. 3. Hood V L and Dunn M J. Urinary excretion of prostaglandin E, and prostaglandin Fza in potassium-deficient rats. Prostaglandins 15: 273-280, 1978. 4. Diising R, Bartter F C, Gill J R jr, Gtillner H G and Lake C R jr. Effects of moderate short-term potassium depletion in normal humans. The role of prostaglandins. Prostaglandins 20: 971-979, 1980. 5. Attallah A A, Stahl R A K, Block D L, Ambrus J L and Lee J B. Inhibition of rabbit renal prostaglandin E, biosynthesis by chronic potassium deficiency. Journal of Laboratory and Clinical Medicine 97: 205-212, 1981. 6. Linas S L and Dickmann D. Mechanism of the decreased renal blood flow in the potassium-depleted conscious rat. Kidney International 21: 757-764, 1982. 7. Rutecki G W, Cox J W, Robertson G W, Francisco L L and Ferris T F. Urinary concentrating ability and antidiuretic hormone responsiveness in the potassium-depleted dog. Journal of Laboratory and Clinical Medicine 100: 53-60, 1982. 8. Nasjletti A, Erman A, Cagen L M, Brooks D P, Crofton J T, Share L and Baer P G. High potassium intake selectively increases urinary PGF,, excretion in the rat. American Journal of Physiology 248: F382-F388,1985. 9. Raymond K H, Lifschitz M D and McKinney T D. Prostaglandins and the urinary concentrating defect in potassium-depleted rabbits. American Journal of Physiology 253: F1113-F1119,1987. 10. Friilich J C, Wilson T W, Sweetman B J, Smigel M, Nies A S, Carr K, Watson J T and Oates J A. Urinary prostaglandins. Identification and origin. Journal of Clinical Investigation 55: 763-770, 1975. 11. FitzGerald G A, Pederson A K and Patron0 C. Analysis of prostacyclin and thromboxane biosynthesis in cardiovascular disease. Circulation 67: 1174-1177.1983. 12. Kirschenbaum M A and Serros E R. Effects of alterations in urine flow rate on prostaglandin E excretion in conscious dogs. American Journal of Physiology 238: F107-Flli, 1980. 13. Walker R M. Brown R S and Stoff J S. Role of renal prostaglandins during antidiuresis and water diuresis in man. Kidney International 21: 365-370, 1981. 14. Lifschitz M D, Epstein M and Larios 0. Relationship between urine flow rate and prostaglandin E excretion in human beings. Journal of Laboratory and Clinical Medicine 105: 234-238, 1985. 15. Roberts D G, Strife R J, Gerber J G, Murphy R C and Nies A S. Effect of sustained water diuresis on prostaglandins E, excretion in humans. American Journal of Physiology 248: F830-F834, 1985.

16. Agnoli G C, Borgatti R, Cacciari M, Garutti C, Ikonomu E, Lenzi P and Marinelli M. Effects of experimental potassium depletion on renal function and urinary prostanoid excretion in normal women during hypotonic polyuria. Clinical Physiology 10: 345-362,199O. 17. O’Connor W J. Normal Renal Function. p. 171. Croom Helm, London, 1982. 18. Seldin D W, Eknoyan G, Suki W N and Rector C J jr. Localisation of diuretic action from the pattern of water and electrolyte excretion. Annals of the New York Academv of Sciences 139: 328-343,1966. 19. Korteweg M, De Boever J, Vandevivere D and Verdonk G. Radioimmunoassay of urinary orostaalandins. pp. 201-206 in Advances in Prostaglandin and Thromboxane Research (B Samuelsson. R Paoletti. P W Ramwell eds) Vol. 6 Raven Press, New York, 1980. 20. Menard J and Catt K J. Measurement of renin activity, concentration and substrate in rat plasma by radioimmunoassay of angiotensin I. Endocrinology 90: 422-430, 1976. 21. Ktirtz A B and Bartter F C. Radioimmunoassay for aldosterone and desoxycorticosterone in plasma and urine. Steroids 28: 133-142, 1976. 22. Wallenstein S, Zucker C L and Fleiss J L. Some statistical methods useful in circulation research. Circulation Research 47: 1-9, 1980. 23. Abbrecht P H and Vander A J. Effects of chronic potassium deficiency on plasma renin activity. Journal of Clinical Investigation 49: 1510-1516, 1970. 24. Brunner H R, Bear L, Sealey J R, Ledingham J G G and Laragh J H. The influence of potassium administration and of potassium deprivation on plasma renin in normal and hypertensive subjects. Journal of Clinical Investigation 49: 2128-2138, 1970. 25. Sealey J E, Clark 1, Bull M B and Laragh J H. Potassium balance and the control of renin secretion. Journal of Clinical Investigation 49: 2119-2127,197O. 26. Cannon P J, Ames R P and Laragh J H. Relation between potassium balance and aldosterone secretion in normal subjects and in patients with hypertensive and renal tubular disease. Journal of Clinical Investigation 45: 865-879, 1966. 27. Luke R G, Wright F S, Fowler N, Kashgarian M and Giebisch G H. Effects of potassium depletion on renal tubular chloride transport in the rat. Kidney International 14: 414-427, 1978. 28. Gutsche H U, Peterson L N and Lavine D Z. In vivo evidence of impaired solute transport by the thick ascending limb in potassium-depleted rats. Journal of Clinical Investigation 73: 908-916, 1984. 29. Luke R G, Booker B B and Galla J H. Effect of potassium depletion on chloride transport in the loop of Henle in the rat. American Journal of Physiology 248: F682-F687,1985. 30. Paller M P, Douglas J G and Linas S L. Mechanism of decreased vascular reactivity to angiotensin II in conscious potassium-deficient rats. Journal of Clinical Investigation 73: 79-86, 1984. 31 Ballermann B J, Levenson D J and Brenner B M. Renin, angiotensin, kinins, prostaglandins and leukotrien&. pp. 307-311 in The Kidney Vol. I (B M Brenner. F C Rector eds) Saunders Co., Philadelphia, 1986. 32. Olsen M E, Hall J E, Montani J P and Cornell J C. Interaction with renal prostaglandins and angiotensin 11 in controlling glomerular filtration in the dog. Clinical Science 72: 429-436, 1986. 33. Stokes J B. Tubular actions of arachidonic acid metabolites. pp. 133-144 in Prostaglandins and the Kidney (M J Dunn, C Patrono, G A Cinotti eds) Plenum Med Book. Co., New York, 1983.

Urinary prostanoid excretion in healthy women with different degrees of induced potassium depletion.

Plasma renin activity (PRA), urinary excretions of PGE2, 6-keto-PGF1 alpha (6KPGF), TXB2 and renal function were determined in healthy women both in n...
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