Racial Microaggressions Mediate the Association Between Posttraumatic Stress and Alcohol Use Among Women of Color Experiencing Intimate Partner Violence.

Objective: Women of Color (WoC) experiencing intimate partner violence (IPV) have elevated rates of posttraumatic stress disorder (PTSD) and alcohol use and related harm (e.g., increased alcohol use and negative consequences). This secondary data analysis assessed the role of racial microaggressions in the association between PTSD and alcohol use and related harm among WoC experiencing IPV. Methods: Participants were 103 WoC currently experiencing IPV and using substances (Mage=40.39, 51.5% Black) who were recruited from the community and completed assessments of PTSD, racial microaggressions, and alcohol use and related harm. Results: Assumptions of Inferiority (e.g., intelligence; B = 1.44, SE = 0.90, 95% CI [0.10, 3.54]) and Environmental Microaggressions (e.g., portrayal in media; B = 1.88, SE = 1.03, 95% CI [0.28, 4.30]) explained the association between PTSD and alcohol use and related harm. Conclusions: Findings underscore the influence of specific microaggressions in the relation between PTSD and alcohol use and related harm among WoC experiencing IPV.

Intervention for marijuana using, court-involved non-incarcerated youth.

INTRODUCTION: Justice-involved youth (JIY) are at elevated risk for substance use and for substance use-related harm compared to non-JIY. Marijuana use is of significant concern in this population, as it is tied to reoffending. Motivational enhancement therapy (MET) and electronic interventions show promise in reducing youth substance use; the degree to which these findings extend to JIY requires additional research attention. Thus, the purpose of this study was to test the preliminary feasibility and effectiveness of a combined brief electronic parenting intervention plus a brief MET-based electronic intervention for JIY adolescents, followed by feedback and development of a change plan with a court worker, on marijuana use. METHODS: Participants were 83 parent-youth dyads recruited from a diversionary family court program who screened positive for past-year marijuana use. At baseline and 3- and 6-month follow-ups, youth self-reported on their substance use, parental monitoring, peer substance use, and dyads completed a discussion task querying parental monitoring, limit setting, and substance use. The study randomized dyads to psychoeducation or the experimental intervention condition post-baseline. The MET-based intervention involved the self-administered e-TOKE (an electronic, marijuana-specific assessment and feedback tool) and a brief follow-up meeting with court staff counselors to review feedback and create a marijuana use change plan. Caregivers completed a computer program aimed at improving parenting and communication with their adolescents. The study administered feasibility and acceptability measures for both conditions. RESULTS: Feasibility of study procedures was demonstrated through recruitment and retention (∼75 % success). Acceptability ratings from youth, parents, and court staff were high and positive. While levels of parental monitoring, as assessed by an observational task, improved over the course of the study, the intervention did not result in a significant change in any of the outcomes tested. CONCLUSIONS: Despite high acceptability and feasibility ratings for the use of an electronic plus in-person MET intervention, reduction of marijuana and other substances was limited for most youth. This suggests that a more intensive intervention, such as stepped care, may be necessary for JIY who are not specifically referred for court proceedings due to marijuana use or those with already well-established use patterns.

Racial/Ethnic Differences in Alcohol and Drug Misuse Among IPV-Victimized Women: Exploring the Role of Difficulties Regulating Positive Emotions.

Alcohol and drug misuse is prevalent and problematic among women who experience intimate partner violence (IPV). Emotional dysfunction has been identified as a key mechanism in the etiology, maintenance, and treatment of alcohol and drug misuse. However, existing research has not considered the role of race/ethnicity in the relations between emotional dysfunction and alcohol and drug misuse. Furthermore, past research in this area has focused almost exclusively on emotional dysfunction stemming from negative (vs. positive) emotions. The goals of the current study were as follows: (a) to explore whether levels of difficulties regulating positive emotions differ among Latina, African American, and White IPV-victimized women, and (b) to examine the moderating role of race/ethnicity in the relations between difficulties regulating positive emotions and alcohol and drug misuse. Participants were 197 IPV-victimized women recruited through the criminal justice system (Mage = 36.14; 51.8% African American, 31.5% White, and 16.8% Latina). Difficulties regulating positive emotions did not differ as a function of race/ethnicity. However, relations among difficulties regulating positive emotions and alcohol and drug misuse were significant for Latina and White but not African American IPV-victimized women. Moreover, race/ethnicity moderated an association between difficulties regulating positive emotions and drug misuse; this relation was significant and positive for White (compared with African American) IPV-victimized women. While preliminary, these results may inform culturally sensitive interventions for alcohol and drug misuse that are tailored to the unique needs of Latina, African American, and White IPV-victimized women.

Exploring the moderating role of gender in the relation between emotional expressivity and posttraumatic stress disorder symptom severity among Black trauma-exposed college students at a historically Black university.

OBJECTIVES: Posttraumatic stress disorder (PTSD) is characterized in part by negative alterations of cognition or mood, including alterations in emotional expressivity, or the extent to which one outwardly displays emotions. Yet, research in this area has relied on predominantly white samples and neglected to consider the potential role of gender, despite there being demonstrated gender differences in both PTSD symptom severity and emotional expressivity, separately. The goal of the current study was to fill a critical gap in the literature by examining the moderating role of gender in the relation between PTSD symptom severity and emotional expressivity in a sample of trauma-exposed Black adults. METHODS: Participants were 207 Black individuals enrolled in a historically Black university in the Southern United States (68.6% female; Mage = 22.32 years). RESULTS: Findings provided support for the moderating role of gender in the association between PTSD symptom severity and emotional expressivity. Specifically, greater PTSD symptom severity was inversely related to emotional expressivity among trauma-exposed Black males and positively associated with emotional expressivity among trauma-exposed Black females. DISCUSSION: These results suggest the potential need for gender-specific assessment and treatment techniques for PTSD symptom severity among trauma-exposed Black college students.

Post-traumatic stress disorder's relation with positive and negative emotional avoidance: The moderating role of gender.

Post-traumatic stress disorder (PTSD) is characterized by avoidance of trauma-related emotions. Research indicates that this avoidance may extend to any emotional experience that elicits distress, including those that are unrelated to the trauma. Literature in this area has been limited in its exclusive focus on negative emotions. Despite evidence of gender differences in PTSD and emotional avoidance separately, no studies to date have examined gender as a moderator of their association. The goal of the current study was to extend research by exploring the moderating role of gender in the relation between PTSD symptom severity and positive and negative emotional avoidance. Participants were 276 trauma-exposed individuals (65.9% female, 65.6% White, Mage = 19.24) from a university in the north-eastern United States. Moderation results indicated a main effect for PTSD symptom severity on both positive (b = 0.07, p < .001) and negative (b = 0.04, p = .03) emotional avoidance. The interaction of gender and PTSD symptom severity was significant for positive emotion avoidance (b = 0.97, p = .01). Analysis of simple slopes revealed that PTSD symptom severity was significantly associated with positive emotional avoidance for males (b = 0.13, p < .001) but not females (b = 0.03, p = .08). Results suggest the importance of gender-sensitive recommendations for assessment and treatment of emotional avoidance in PTSD.

Rat NKCC2/NKCC1 cotransporter selectivity for loop diuretic drugs.

It is generally assumed that bumetanide possesses some selectivity for the renal Na-K-Cl cotransporter NKCC2, although the results are scarce in the literature and comparisons were done with extra-renal NKCC1 at its basal, almost silent state. Here we investigated NKCC2/NKCC1 selectivity of loop diuretic drugs (bumetanide, piretanide and furosemide) as a function of the NKCC1 activated state (NKCC1 was activated by hypertonic media). NKCC2 activity was measured in isolated rat medullary thick ascending limb (mTAL) and NKCC1 in rat thymocytes and erythrocytes. When NKCC2 was compared with NKCC1at its activated state, all three diuretic drugs inhibited NKCC2 and NKCC1 with the same potency (bumetanide pIC50=6.48, 6.48 and 6.47; piretanide pIC50=5.97, 5.99 and 6.29; and furosemide pIC50=5.15, 5.04 and 5.21 for mTAL NKCC2, erythrocyte NKCC1 and thymocyte NKCC1, respectively). Basal NKCC1 exhibited a lower diuretic sensitivity, although with marked differences depending on the diuretic drug and the cell type in consideration and with the notable exception of furosemide in erythrocytes. Molecular modelling showed that bumetanide and piretanide possess four potentially active groups, of which three are shared with furosemide at similar intergroup distances. Of these three common groups, one should not bind to basal NKCC1 in thymocytes. The fourth (phenoxy) group (absent in furosemide) confers higher lipophilicity and should not bind to basal NKCC1 in erythrocytes. In conclusion, loop diuretics had no NKCC2/NKCC1 selectivity, when NKCC1 is measured at its activated state. Basal NKCC1 has a reduced diuretic sensitivity, of very different magnitude depending on the diuretic drug and cell type in consideration.

The erythrocyte Na,K,Cl cotransporter and its circulating inhibitor in Dahl salt-sensitive rats.

BACKGROUND: Abnormal Na,K,Cl cotransport is thought to be a pathogenic factor in Dahl salt-sensitive rat models, but the only direct evidence for this is an increased cotransport activity found in erythrocytes from salt-loaded Dahl salt-sensitive rats. OBJECTIVE: To re-examine erythrocyte cotransport fluxes and a circulating cotransport inhibitory factor (CIF) in inbred Dahl rats maintained on a low (0.2%) salt diet. Cotransport fluxes were investigated both under basal conditions and after stimulation by cell shrinking. METHODS: Blood was drawn from 12 male Dahl salt-sensitive and 12 Dahl salt-resistant rats of the inbred John Rapp strain. Erythrocyte Na,K,Cl cotransport activity was equated to the bumetanide-sensitive fluxes of sodium, rubidium or lithium. Plasma CIF activity was tested in human erythrocytes. RESULTS: In Dahl salt-sensitive rats: (1) plasma CIF activity (5.7+/-0.4 units/ml) was modestly higher than in Dahl salt-resistant rats (2.97+/-0.12 units/ml, P < 0.0001), but much lower than that previously found in salt-loaded Dahl salt-sensitive rats (16.1 units/ml), and (2) erythrocytes exhibited a similar bumetanide-sensitive sodium efflux (rate constant 0.056+/-0.008 h(-1)) as in Dahl salt-resistant rats (0.047+/-0.007 h(-1)). Following hypertonic shock, the bumetanide-sensitive rubidium influx reacted more to cell shrinkage in Dahl salt-sensitive than in Dahl salt-resistant erythrocytes (cell volume decrease required to stimulate bumetanide-sensitive rubidium influx by 4000 micromol/l cells per h=-4.04+/-0.36 versus -5.89+/-0.44 fl, respectively; P< 0.01). CONCLUSIONS: When fed a low-salt diet, Dahl salt-sensitive rats present slightly increased plasma CIF levels and normal erythrocyte cotransport fluxes under basal conditions, but an increased response to a hypertonic shock. Therefore, if there is any primary cotransport abnormality in Dahl salt-sensitive rats, it appears to be restricted to the renal Na,K,Cl cotransporter BSC1 isoform. Alternatively, any such change may be the consequence of abnormal regulation by osmolarity-dependent mechanisms.

Regulation of renal Na-K-Cl cotransporter NKCC2 by humoral natriuretic factors: relevance in hypertension.

A furosemide-sensitive Na-K-Cl cotransporter (NKCC2 isoform) accounts for almost all luminal NaCl reabsorption in the thick ascending limb of Henle's loop (TALH). The activity of this transport protein is regulated by humoral factors (CIF: cotransport inhibitory factors). One family of CIF compounds is represented by the urinary phytoestrogens equol and genistein, which inhibit cotransport fluxes at similar concentrations as furosemide. Moreover, they possess similar salidiuretic potency as furosemide in the isolated perfused rat kidney, but are less potent than furosemide in vivo. Thus, dietary phytoestrogens can be responsible, at least in part, for the low blood pressure of vegetarians. A second type of CIF is represented by a circulating and urinary factor which is evoked by salt-loading. This, which is not a "ouabain-like" factor, appears to be a new retropituitary natriuretic compound. Endogenous CIF is increased in hypertensive Dahl salt-sensitive rats, probably as a compensatory mechanism against the enhanced NaCl reabsorption in the TALH, which characterizes this model of hypertension. Finally, chronic excess of circulating CIF inhibits and induces up-regulation of erythrocyte Na-K-Cl cotransporter NKCC1.

Endogenous sodium-potassium-chloride cotransport inhibitor in congestive heart failure.

OBJECTIVES: This study sought to evaluate the relation, if any, between fluid overload in congestive heart failure (CHF) and a newly discovered endogenous natriuretic factor acting like loop diuretic drugs: cotransport inhibitory factor (CIF). BACKGROUND: The humoral mechanisms regulating volume overload in CHF are not fully understood. Therefore, we investigated whether there is a role for CIF in this pathologic condition. METHODS: Plasma and urinary CIF levels were investigated in 23 patients with chronic CHF and compared with changes in plasma atrial natriuretic peptide (ANP). Twelve patients without CHF served as control subjects. RESULTS: CHF was associated with a highly significant threefold increase in both plasma CIF levels (mean +/- SD 7.10 +/- 3.01 vs. 2.28 +/- 0.92 U/ml, p < 0.0001) and urinary CIF excretion (7,849 +/- 3,600 vs. 2,351 +/- 1,297 U/day, p < 0.0001) with respect to patients without CHF. CIF increased as a function of impairment in left ventricular ejection fraction (r = -0.703, p < 0.0001) and the severity of clinical status. Plasma ANP was also increased in patients with CHF, although to a lesser extent (68%, p = 0.0501) than plasma CIF, and was also significantly correlated with left ventricular ejection fraction (r = -0.552, p = 0.0004). CONCLUSIONS: Plasma and urinary CIF activities were strongly and very significantly increased in chronic CHF. In addition to ANP, this long-term natriuretic agent may be of potential importance in reducing fluid overload in CHF.

[A new natriuretic factor acting like loop diuretics. Kinetics in normal and hypertensive rats]. / Un nouveau facteur natriurétique agissant comme les diurétiques de l'anse. Comportement cinétique chez le rat normal et hypertendu.

We have recently described that urines from salt-loaded rats contain a potent natriuretic factor acting at the Na-K-Cl cotransport system (CIF: "Cotransport Inhibitory Factor"). Here we investigated the kinetics of the urinary CIF excretion which follows an oral salt-load: (i) in normal rats, relative to that of the atrial natriuretic peptide (ANP) and (ii) in an experimental model of salt-dependent genetic hypertension (Dahl's rats). Thus, Wistar rats were orally loaded with 2% NaCl for 8 days. Urinary CIF excretion was measured by testing the inhibitory potency of urines on bumetanide-sensitive lithium efflux in lithium-loaded human erythrocytes. Plasmatic levels of ANP were measured by radioimmunoassay. Plasma ANP rapidly and transiently increased during the first 24 hs of salt-load, decreasing thereafter down to normal levels in 6-8 days. Conversely, CIF slowly increased after 24 hs up to maximal constant levels after 5 days of salt-loading. Dahl salt-sensitive rats exhibited highly significant increases in urinary CIF excretion with respect to salt-resistant rats. In the basal state (before salt-loading) urinary CIF excretion was 101 +/- 13 vs 17.6 +/- 4.5 units/day in salt-sensitive vs. salt-resistant rats (n = 7 for each group, p < 0.001). This difference was maintained after salt loading (3 380 +/- 990 vs. 456 +/- 159 units/day, p < 0.05 at day 5).(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of Na-K-Cl cotransport fluxes and salidiuretic action by an urinary extract of salt-loaded rats.

We previously found a potent inhibitor of the Na-K-Cl cotransport system in urines from salt-loaded rats (C.I.F. = cotransport inhibitory factor, ref. 1). Here we extracted an urinary fraction (approximately 1% urine dry weight), free from immunoreactive A.N.P. and digoxin activity, which: (i) potently inhibited cotransport fluxes in MDCK (Madin and Darby canine kidney] cells and in human erythrocytes, (ii) inhibited Na(+)-dependent chloride/bicarbonate exchange with 2-3 times less potency than cotransport and (iii) strongly increased natriuresis and diuresis after i.v. infusion in rats with no significant change in kaliuresis (salidiuretic action reduced by probenecid). Therefore, C.I.F. seems to be a new natriuretic factor with part, but not all the biological profile of loop diuretic drugs.

Opposite effects of cell growth factors and cicletanine sulfate on the sodium-independent [Cl-/HCO3-] exchange in cultured vascular smooth muscle.

Cicletanine sulfate was tested on bicarbonate-dependent pHi changes in cultured vascular smooth muscle (A10 line). Cicletanine sulfate exhibited double reactivity with regard to the cell alkalinization induced by bicarbonate uptake. The analysis of 11 concentration-response curves revealed a high reactivity component (IC50 approximately 3.5 x 10(-8) mol/L) and a weak reactivity component (IC50 approximately 4 x 10(-4) ml/L). Regarding the cell acidification induced by bicarbonate extrusion, cicletanine sulfate exhibited a single high reactivity component (IC50 = 5.9 +/- 2.9 x 10(-7) mol/l; mean +/- SD, n = 7). The high and weak reactivity sites were both sensitive to DIDS. Analysis of the data strongly suggested that the highly reactive site corresponds to a sodium-independent (Cl-/HCO3-] exchanger, which catalyzes net bicarbonate efflux, and the weak-reactivity site corresponds to the inwardly directed sodium-dependent [Cl-/HCO3-] exchanger. Three cell growth factors--epidermal growth factor, arginine-vasopressin, and insulin--were able to stimulate the sodium-independent [Cl-/HCO3-] exchanger in A10 cells. Finally, cicletanine sulfate (30 mumol/L) partially inhibited serum-dependent A10 cell growth. In conclusion, cicletanine sulfate and cell growth factors exert opposite effects (inhibition and stimulation, respectively) on the sodium-independent [Cl-/HCO3-] exchanger in cultured vascular smooth muscle. The effect of cicletanine sulfate on the sodium-independent [Cl-/HCO3-] exchanger may account for the ability of cicletanine to favorably alter vascular pathology in spontaneously hypertensive rat (SHR) models.

[Liddle syndrome (or pseudo-hyperaldosteronism). Long-term development and erythrocyte potassium flow study in 4 cases]. / Syndrome de Liddle (ou pseudo-hyperaldostéronisme). Evolution à long terme et étude des flux potassiques érythrocytaires dans 4 observations.

BACKGROUND: Liddle's syndrome (or pseudoprimary aldosteronism) is a rare hereditary disease; only 18 cases have been reported since 1963. Its cause remains unclear, but one of its features is increased cell membrane permeability to ions. PATIENTS AND METHODS: A diagnosis of Liddle's syndrome was made in 4 new cases, all female, two of them sisters (cases n0 3 and 4), at the ages of 2, 12, 5 and 4 years. The first manifestations were dehydratation with hypokalemia at 6 months (case n0 1), hypertension at 2 years (case n0 2), polydipsia with poor weight and height gain at 5 and 4 years of age (cases n0 3 and 4). At diagnosis, all the patients had severe hypertension, metabolic alkalosis, hypokalemia and hyperkaliuria, low plasma renin activity and serum aldosterone levels. Administration of antihypertensive agents was without effect, but the hypertension was reduced when triamterene and low-sodium diet were used. Hypercalciuria was observed in 2 cases and nephrocalcinosis in 2 (case n0 1 had both hypercalciuria and nephrocalcinosis). The 2 oldest patients (n0 3 and 4) developed progressive kidney failure, possibly due to reno-vascular disease secondary to hypertension. Patient n0 3 underwent kidney transplantation 18 years after the first symptoms of the disease. This resulted in the complete disappearance of her hypokalemia and hypertension. The red blood cell membrane permeability to K+ and Cl- was studied in all 4 cases before triamterene treatment. The passive permeability to K+ and (K+/Cl-) cotransport were both elevated. A second study, 3 years (cases n0 2 and 3) and 8 years (cases n0 1 and 4) later, of patients treated with triamterene showed low values for passive K+ permeability and (K+/Cl-)-cotransport. CONCLUSIONS: The 4 new cases of Liddle's syndrome had the classic features of the disease, except for hypercalciuria and nephrocalcinosis in 2 of them. The cell membrane permeability data are difficult to interpret. Hypokalemia and hypertension were immediately corrected after kidney transplantation in one case and remained so for 4 years, suggesting that this disease is tubular in origin.

Cicletanine sulfate: inhibition of anion transport systems and natriuretic activity.

In contrast with cicletanine, its urinary sulfoconjugate metabolite (cicletanine sulfate) was active on membrane ion transport in human red blood cells. Cicletanine sulfate was a more potent inhibitor of the Na+ dependent [Cl-/HCO3-] exchanger (IC50 = 9 +/- 3 x 10(-5) mol/l; mean +/- SD of 4 experiments) than cicletanine (IC50 = 10(-3) mol/l). This inhibitory potency was intermediate between that of xipamide (IC50 = 2 x 10(-5) mol/l) and that of furosemide (IC50 = 2 x 10(-4) mol/l). Moreover, cicletanine sulfate exhibited modest inhibitory potency against the [Na+,K+,Cl-]-cotransport system (IC50 = 1 +/- 0.3 x 10(-3) mol/l; mean +/- SD of 4 experiments) and poor inhibitory activity against the [K+,Cl-]-cotransport system. Cicletanine sulfate was unable to modify the activity of Cl(-)-independent membrane carriers (Na+:H+ exchanger, Ca2+ pump, Na+:Li+ countertransport system and Na+,K+ pump). Following renal intraarterial administration in rats, cicletanine sulfate and not cicletanine, exhibited salidiuretic activity. In conclusion, the urinary sulfo-conjugate of cicletanine is an active anion transport inhibitor and natriuretic metabolite. In fact, this metabolite may be responsible for the salidiuretic action of cicletanine.

Evidence for the O-sulfo derivative of MK-447 as active metabolite of MK-447.

In contrast with furosemide (and other sulfamoylbenzoic and aryloxyacetic acids loop diuretics), MK-447 was unable to inhibit the [Na+,K+,Cl-] cotransport system in human red blood cells. Indeed, this compound was a very poor ion transport inhibitor (inactive on Ca(2+)-sensitive K+ channels, the Ca2+ pump, the Na+:Mg2+ exchange, the Na+:Li+ countertransport system and the [K+,Cl-] cotransport system, and only inhibiting the [Cl-/HCO3-] exchanger and the Na+,K+ pump at high concentrations). Conversely, its urinary metabolite (O-sulfo)-MK-447 was a very potent inhibitor of the [Na+,K+,Cl-] cotransport system (IC50 of 1.6 +/- 0.5 x 10(-6) M; mean +/- S.D. of four experiments). This compound was a much more potent [Na+,K+,Cl-] cotransport inhibitor than furosemide, and almost as active as bumetanide. In addition, (O-sulfo)-MK-447 was a moderate inhibitor of the [Cl-/HCO3-] exchanger (IC50 of 6 +/- 3 x 10(-5) M, n = 3), its potency being intermediate between that of xipamide and that of furosemide. Interestingly, it exhibited some inhibitory activity against Ca(2+)-sensitive K+ channels but only at high concentrations (it had no effect on the [K+,Cl-] cotransport system, the Ca2+ pump or the Na+:Mg2+ exchanger). The results suggest strongly that the O-sulfo derivative of MK-447 is an active natriuretic metabolite of MK-447. This metabolite may be responsible for the salidiuretic action of MK-447.

CRE 10904 [2-(p-fluorophenoxy), 1-(o-hydroxyphenyl)-ethane]: a new diuretic and antihypertensive drug acting by in vivo sulfation.

CRE 10904 [2-(p-fluorophenoxy), 1-(o-hydroxyphenyl)-ethane, the leading compound of a new family of loop diuretic and antihypertensive agents: 1-aryl, 2-aryloxy-ethanes] induced high-ceiling natriuretic action in dogs and rats, but was completely inactive in pigs. High-performance liquid chromatography determinations revealed that all CRE 10904 (p.o. or i.v. administered) was rapidly sulfo-conjugated in dogs and rats, and glucurono-conjugated in pigs. The (O-sulfonyl)-CRE10904 metabolite (or simply CRE 11296) rapidly appeared in plasma, reached a concentration peak at about 40 min and disappeared with a half-life time of about 3 hr. The urinary excretion of CRE 11296 was correlated with the natriuretic activity of CRE 10904. Moreover, CRE 11296 was a powerful natriuretic compound in rats and dogs and, even in pigs, i.v. CRE 11296 induced transient natriuresis (just before its rapid hydrolysis and glucurono-conjugation). Studies in human red blood cells revealed that: 1) CRE 11296 was a potent inhibitor of the [Na+,K+,Cl-]-cotransport system (IC50 of 1.5 +/- 0.3 x 10(-5) M; mean +/- S.E.M. of 5 experiments), slightly more powerful than furosemide (IC50 of 2 x 10(-5) M), 2) it was the only diuretic drug potently inhibiting the [K+,Cl-]-cotransport system (IC50 of 2.1 +/- 0.6 x 10(-5) M; N = 3) and the [Cl/HCO3-] exchanger (IC50 of 4.5 +/- 1.0 x 10(-5) M; N = 3) and 3) CRE 10904 and its glucuronide were much less potent Cl- transport inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)