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At least 271 records · Page 15Linked to original sources
PubMed1984

Systolic blood pressure responses to enalapril maleate (MK 421, an angiotensin converting enzyme inhibitor) and hydrochlorothiazide in conscious Dahl salt-sensitive and salt-resistant rats.

Systolic blood pressure responses to enalapril maleate (MK 421, a new angiotensin converting enzyme inhibitor (CEI] and hydrochlorothiazide (HTZ) were studied in conscious Dahl salt-sensitive (DS) and salt-resistant (DR) rats maintained on a high salt (8.0% NaCl) and a normal salt (0.4% NaCl) diet. The DS rats were severely hypertensive after 3 weeks on the high salt diet whereas the systolic blood pressure (SBP) of the DR rats were normotensive. Oral treatment with enalapril (15-100 mg X kg-1 X day-1) and HTZ (60-400 mg X kg-1 X day-1) caused a significant reduction of SBP in the DS rats with the high salt diet (P less than 0.001); however, this was not observed until after 4 weeks of treatment when the dosage was 30 and 150 mg X kg-1 X day-1, respectively. Furthermore, enalapril therapy alone significantly reduced the SBP of all groups of rats regardless of diet or Dahl strain (P less than 0.001), but this was not observed until the end of the 7th week of therapy in DR rats on 8.0% NaCl and the end of the 3rd week of therapy for DR and DS rats on 0.4% NaCl. These results suggest that enalapril may lower SBP by mechanisms other than those related to an action as a CEI.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2005

Links between dietary salt intake, renal salt handling, blood pressure, and cardiovascular diseases.

Epidemiological, migration, intervention, and genetic studies in humans and animals provide very strong evidence of a causal link between high salt intake and high blood pressure. The mechanisms by which dietary salt increases arterial pressure are not fully understood, but they seem related to the inability of the kidneys to excrete large amounts of salt. From an evolutionary viewpoint, the human species is adapted to ingest and excrete <1 g of salt per day, at least 10 times less than the average values currently observed in industrialized and urbanized countries. Independent of the rise in blood pressure, dietary salt also increases cardiac left ventricular mass, arterial thickness and stiffness, the incidence of strokes, and the severity of cardiac failure. Thus chronic exposure to a high-salt diet appears to be a major factor involved in the frequent occurrence of hypertension and cardiovascular diseases in human populations.

Animals↗
PubMed2006

Different effects of angiotensin receptor blockade on end-organ damage in salt-dependent and salt-independent hypertension.

BACKGROUND: Although angiotensin II type 1 receptor blockers have emerged as effective antihypertensive agents, it is not known how efficacious these agents are in treating hypertension-associated target organ damage. METHODS AND RESULTS: The present study was undertaken to compare the effect of angiotensin type 1 receptor inhibition on the progression of the organ damage observed in 2 models of hypertension, namely, salt-sensitive and nitric oxide synthase inhibition-mediated hypertension. Effective (16.4 micromol/kg) and ineffective (0.8 to 4.9 micromol/kg) antihypertensive doses of candesartan cilexetil were initiated after hypertension was established. Both low- and high-dose candesartan cilexetil significantly reduced cardiac and renal damage in the nitric oxide synthase inhibitor model of hypertension (P < 0.05 versus untreated); however, high-dose candesartan caused a significant increase in renal damage in the Dahl salt-sensitive model of hypertension (P < 0.05 versus untreated). Interestingly, the beneficial end-organ effects of candesartan in the nitric oxide synthase inhibition model were independent of sustained antihypertensive actions of candesartan, whereas the exacerbation of renal injury with candesartan in the Dahl salt-sensitive model was inversely related to its blood pressure-lowering effect. CONCLUSIONS: These data show that angiotensin type 1 blockade reduces injury in the l-nitroarginine methyl ester model but increases tissue injury in the salt-sensitive model. These data suggest that angiotensin II via angiotensin type 1 receptor activation contributes to organ damage in nitric oxide-deficient salt-independent hypertension but is protective in salt-induced hypertension. These data further suggest that (1) renal injury may evolve independently of blood pressure and (2) the effectiveness of an antihypertensive agent in ameliorating renal injury may depend on the etiology of the hypertension.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2003

Salt loading affects cortisol metabolism in normotensive subjects: relationships with salt sensitivity.

We studied cortisol metabolism together with insulin sensitivity [homeostatic model assessment (HOMA)] and renal hemodynamics in 19 salt-resistant (sr) and nine salt-sensitive (ss) normotensive subjects after a low- and high-salt diet. Results are described as high- vs. low-salt diet. Sum of urinary cortisol metabolite excretion (sum(metabolites)) increased in sr subjects (3.8 +/- 1.6 vs. 3.1 +/- 1.1 microg/min per square meter, P < 0.05) and decreased in ss subjects (2.3 +/- 1.0 vs. 2.9 +/- 1.1 microg/min per square meter, P < 0.05). Plasma 0830 h cortisol decreased in sr subjects but did not change significantly in ss subjects. In all subjects, the absolute blood pressure change correlated negatively with the percentage change in sum(metabolites) (P < 0.05) and positively with the percentage change in renal vascular resistance (P < 0.05). Sum(metabolites) during high-salt diet correlated negatively with the percentage changes in plasma 0830 h cortisol (P < 0.05) and renal vascular resistance (P = 0.05). HOMA did not change in either group, but the percentage change in HOMA correlated positively with the percentage change in plasma cortisol (P = 0.001) and negatively with the percentage change in sum(metabolites) (P < 0.01). Parameters of 11 beta-hydroxysteroid dehydrogenase activity were not different between groups and did not change. In conclusion, these data suggest that cortisol elimination is affected differently after salt loading in sr and ss subjects. Changes in circulating cortisol might contribute to individual sodium-induced alterations in insulin sensitivity.

17-Hydroxysteroid Dehydrogenases↗
PubMed1996

Restoration of endothelial cell function by chronic cicletanine treatment in Dahl salt-sensitive rats with salt-induced hypertension.

The effects of chronic cicletanine (CICL) treatment on endothelial cell function were investigated in Dahl salt-sensitive (Dahl S) rats. Forty-four six-week-old Dahl S rats were divided into four groups: i) 10 Dahl S rats fed a low-salt (0.3% NaCl) diet and given vehicle, ii) 12 Dahl S rats fed a high-salt (4% NaCl) diet and given vehicle, iii) 11 low-dose (10 mg/kg body weight/d) CICL-treated Dahl S rats fed a high-salt diet, and iv) 11 high-dose (30 mg/kg body weight/d) CICL-treated Dahl S rats fed a high-salt diet. The rats were maintained on the respective salt regimen for 12 wk and treated with cicletanine for the last 6 wk, after which various parameters of endothelial cell function were determined. Systolic blood pressure, measured by the tail-cuff method, was reduced significantly by high-dose cicletanine (223 vs. 195 mmHg, p < 0.01). Scanning electron microscopy revealed that high-dose CICL attenuated endothelial injury in the aorta of Dahl S rats. Arterial lesions in the heart and glomerulosclerosis in the kidney were significantly reduced by treatment with high-dose CICL. Moreover, prostacyclin (PGI2) and prostaglandin E2 (PGE2) generation in the aortic wall was significantly increased by 28% (p < 0.005) and by 149% (p < 0.001), respectively, by high-dose CICL. Nitric oxide (NO) generation in the aortic walls was significantly increased by high-dose CICL (0.38 vs. 15.4 pmol/cm2/30 min, p < 0.001). This effect was accompanied by a 47% increase in cGMP synthesis in the vascular walls. In contrast, the synthesis of PGI2, PGE2, and NO in the kidney slices did not differ significantly among the four experimental groups. In addition, the generation of vasodilatory substances inversely correlated with the score of vascular lesions in the heart and kidney. The results suggested that the blood pressure reduction by chronic cicletanine treatment in Dahl S rats is associated with an improvement in endothelial cell function. The increased release of vasodilatory substances from endothelial cells may contribute to the blood pressure reduction and attenuation of vascular injury observed with cicletanine treatment.

Animals↗
PubMed2001

Sodium chloride loading does not alter endothelium-dependent vasodilation of forearm vasculature in either salt-sensitive or salt-resistant patients with essential hypertension.

The purpose of this study was to determine whether a high NaCl intake impairs endothelium-dependent and -independent vasodilation of forearm circulation in salt sensitive (SS) patients with essential hypertension. We evaluated the effects of intra-arterial acetylcholine (ACh) and isosorbide dinitrate (ISDN) on forearm hemodynamics in 29 patients with essential hypertension, while consuming a low NaCl (50 mmol/d) or high Na Cl (340 mmol/d) diet for 1 week. The forearm blood flow (FBF) was measured by strain-gauge plethysmography. Patients were classified as SS (n=12) or salt resistant (SR; n=17) based on salt-induced changes in blood pressures. The FBF responses of ACh and ISDN were similar in the SS and SR patients while on either NaCl diet, and was not altered by salt loading (ACh, SS: low NaCl 22.8+/-4.3 vs. high NaCl 21.1+/-3.6 ml/min per 100 ml, SR: low NaCl 22.5+/-4.0 vs. high NaCl 23.3+/-4.1 ml/min per 100 ml; ISDN, SS: low NaCl 13.9+/-2.1 vs. high NaCl 14.1+/-2.2 ml/min per 100 ml, SR: low NaCl 13.8+/-2.3 vs. high NaCl 14.0+/-2.2 ml/min per 100 ml). There were no significant differences in the vascular responses to ACh and ISDN in the presence of N(G)-monomethyl-L-arginine, a nitric oxide synthase inhibitor, in either group for either NaCl diet. These findings suggest that forearm resistance artery endothelial function may not be influenced by salt loading in either SS patients which finding may play a role in determining salt sensitivity in patients with essential hypertension or SR patients.

Diet, Sodium-Restricted↗
PubMed1990

Japanese dietary intake of salt and protein--relating to the strategy of salt restriction.

The high level of Japanese salt intake, which has been the major risk factor for cerebrovascular disease and hypertension, has decreased since World War II, and reached a steady level. In the present study, the dietary salt intake in Tohoku (once the district of highest sodium intake) and that in Kyushu (once the district of median or low sodium intake) were studied in relation to nutritional status by the analysis of sodium and urea-nitrogen excretion in 24-hr urine samples collected from 305 healthy Japanese. When the amount of urinary creatinine and urea-nitrogen were adjusted, the mean value of urinary sodium in females was significantly larger in Tohoku than in Kyushu, but not significantly in males. The regional difference of salt intake still remains, although it seems to be disappearing. Traditionally, Japanese high intake of salt was accompanied by poor nutritional status. In the present study, however, a significant positive correlation was observed between sodium and urea-nitrogen. The excess of protein intake would cause the excess of salt intake. Therefore, the strategy of further salt restriction should be directed to not only traditional salty foods but also nutritional status such as protein intake.

Age Factors↗
PubMedDate not supplied

Prediction and consistency of blood pressure salt-sensitivity as assessed by a rapid volume expansion and contraction protocol. Salt-Sensitivity Study Group of the Italian Society of Hypertension.

BACKGROUND: This multicenter trial in essential hypertensive patients (n=94) is aimed i) to evaluate the distribution of blood pressure salt-sensitivity by a rapid volume expansion/contraction protocol over three days; ii) to investigate the within-patient reproducibility and to identify predictors of the response to the test; iii) to compare this response with the response to dietary NaCl restriction. METHODS: The study design included: 1) screening for salt-sensitivity by the rapid test; 2) a controlled trial of dietary salt restriction; 3) repetition of the rapid test in a subgroup of patients. RESULTS: The mean BP response to the rapid test fitted a Gaussian curve. In multivariate regression analysis, controlling for the effect of potential confounders, the blood pressure increment during the intravenous saline infusion was the best independent predictor of the response to the test (r=0.713) with minor contributions by the 24-h urinary sodium excretion before the test and by baseline fasting serum insulin. These three variables together explained 61% of the overall variability of the response. The Spearman rank correlation coefficient between the BP response to the rapid test and the response to the dietary protocol was 0.21, p=0.05. Upon repetition of the rapid test, the correlation coefficient between the responses observed on the two occasions was 0.60 (n=19, p<0.01); there were no patients misclassified across the extreme tertiles of the distribution of salt-sensitivity. CONCLUSION: We conclude that the rapid test reproducibly identified patients in the upper and lower parts of the distribution of salt sensitivity. The analysis of possible predictors of the response to the test suggested that the evaluation of the blood pressure response to saline infusion, upon careful standardization of dietary NaCl intake, may represent an alternative to the completion of the whole test for the screening of the salt-sensitivity.

Adult↗
PubMed2000

The effect of high salt intake on the mandibular bone loss in Dahl-Iwai salt-sensitive rat.

The purpose of this study was to evaluate the effect of high salt intake on the mandibular bone in Dahl-Iwai salt-sensitive (DS) rats. Twenty-eight 11-week-old male DS rats were divided into four groups (n=7). The control groups received a normal (0.2% NaCl) diet while the experimental groups received a diet supplemented with 8.0% NaCl. The systolic blood pressure was significantly increased in the experimental groups compared to the control groups. The animals were sacrificed under ether anesthesia at the 8th week or the 22nd week of the experiment. The biochemical data in plasma and urine suggested negative calcium balance in the experimental groups compared to the control groups. The bone mineral density was significantly reduced at the 22nd week of high salt loading. The histomorphometric analysis suggested that the reduction of the mandibular bone volume had already started by the 8th week of high salt loading along with the increased bone resorption and the decreased bone formation, and that the improper bone remodeling balance became normalized by the 22nd week of high salt loading. In conclusion, these results indicate that a high salt intake causes not only severe hypertension but also a mandibular bone reduction in the DS rats.

Absorptiometry, Photon↗
PubMed2005

Polymorphism in Nos2 gene is absent in Prague colony of Dahl/Rapp salt-sensitive and salt-resistant rats.

We have searched for polymorphism of inducible nitric oxide synthase gene (Nos2 gene) in the Prague colony of salt-sensitive and salt-resistant Dahl/Rapp rats. Specific primers were used to confirm previously described Nos2 gene polymorphism because this gene was suggested to be a potential candidate gene for genetic hypertension. Phenotyping (blood pressure, organ weight, plasma lipids) have confirmed the data known from other colonies of Dahl/Rapp rats. However, in our colony we were not able to find any Nos2 gene polymorphism between salt-sensitive and salt-resistant rats, which was previously described in animals from Harlan colony. Moreover, the genetic homogeneity of our salt-sensitive and salt-resistant rats in terms of Nos2 gene was the same as in the original Brookhaven colony of Dahl rats. This is surprising because our colony has been established from breeding pairs kindly provided by Prof. J.P. Rapp more than 15 years ago. It seems that the polymorphism found in Harlan colony could be the result of previous contamination or genetic drift during the breeding conditions specific for this colony.

Animals↗
PubMed2005

Decolorization of azo dyes with high salt concentration by salt-tolerant mixed cultures under anaerobic conditions.

Because the lack of detailed study of biological decolorization in high salt dye wastewater, it is still difficult to evaluate the biological treatment on high-salinity dye wastewater. The experiments were carried out to study the salt-tolerant bacteria, which is useful in the treatment of high-salinity colored wastewater. Simulated wastewater containing 5-150 g/L salt (NaCl) and 50-2000 mg/L Reactive Brilliant Red K-2BP was treated with three salt-tolerant mixed cultures (CAS, TAS, DSAS), which were under a gradually acclimated procedure. With the increase of concentrations of salt and dye, the decolorization became low. The abilities of decolorization of dyes wastewater by three mixed cultures (CAS, TAS, DSAS) were studied, CAS and DSAS mixed cultures showed more active for the treatment of high-salinity colored wastewater than TAS mixed cultures. The results suggested that there might be a simple process for the high salt wastewater treatment, which could be incorporated into conventional activated sludge plants.

Azo Compounds↗
PubMed1991

Heterogeneity of blood pressure responses to salt restriction and salt appetite in rats.

In contrast to a widely held belief, the response of blood pressure to even marked changes of salt (NaCl) intake is extremely heterogeneous in different strains of laboratory rats. Like in healthy humans, it is rather difficult to induce an increase or a decrease of blood pressure in normotensive rats by the manipulation of dietary salt consumption within a reasonable range. Moreover, severe NaCl restriction is sometimes associated with a paradoxical rise in blood pressure. No direct relation appears to exist between salt appetite and blood pressure. We showed that salt appetite was increased after dietary NaCl restriction in normotensive Wistar rats compared with normotensive Fischer 344 rats. The latter had a high renin status which was not sensitive to changes in dietary salt. An altered peripheral or central renin metabolism in this rat strain might be partly responsible for their relative lack of salt appetite and could be related to their notable lack of blood pressure sensitivity to dietary NaCl.

Animals↗
PubMed1988

Stimulatory and inhibitory effects of sodium salts on adenylate cyclase of rat liver. Implications for salt modulation of guanine nucleotide-binding regulatory component function.

We have examined the effects of sodium (Na+) salts on rat liver adenylate cyclase. Increasing concentrations of Na+ salts produced biphasic stimulation and inhibition of adenylate cyclase and potentiated enzyme activation by GTP and its hydrolysis resistant analog 5'-guanylyl imidodiphosphate. Salt effects were temperature dependent, of rapid onset, and specific for the Na+ cation though also partly dependent on the accompanying anion. Sodium salt stimulation of adenylate cyclase and enhancement of GTP activation were attenuated by agents (pertussis toxin and N-ethylmaleimide) which inactivate the inhibitory guanine nucleotide-binding regulatory component (Gi) of adenylate cyclase. Cholera toxin, which activates the stimulatory guanine nucleotide-binding regulatory component (Gs) of adenylate cyclase and thereby increases enzyme activity, augmented the inhibitory phase of Na+ salt action. These results suggest that the stimulatory and inhibitory effects of Na+ salts may be due, respectively, to inhibition of Gi and Gs modulation of adenylate cyclase.

Adenylate Cyclase Toxin↗
PubMed1987

Circaseptan rhythm in sodium and potassium excretion in salt-sensitive and salt-resistant Dahl rats.

Six salt-sensitive (S) and six salt-resistant (R) male Dahl rats were housed in metabolic cages under LD 12:12 (L 0600-1800). High-salt (8%) and low-salt (0.4%) diets were available to half the S and R rats, respectively for 4 hr during a 24-hr span (feeding 1800-2200). Urine was collected at 4-hr intervals for 30 days. Sodium and potassium were determined by ion-specific electrode. Apart from circadian rhythmicity, a circaseptan rhythm in sodium and potassium excretion came to the fore in the rats on the high-salt diet only, with a phase difference of about 180 degrees between sodium and potassium. These rhythms were not detectable in the animals eating their usual-low salt diet. The ability to induce circaseptan variations in renal function may lend itself to the chronotherapeutic utilization of such cycles in achieving optimal therapeutic effects or minimizing undesirable side effects of different forms of treatment.

Animals↗
PubMed1984

Immunological responses to complex salts of platinum. II. Enhanced IgE antibody responses to ovalbumin with concurrent administration of platinum salts in the rat.

The effect of platinum group metal salts on IgE antibody synthesis in an animal model was studied with respect to the magnitude and kinetics of the response. In outbred Hooded Lister Rats immunized with 10 micrograms ovalbumin with B. pertussis as adjuvant and boosted with 1 microgram in saline an enhanced secondary response to ovalbumin was obtained when certain halide platinum salts were given concurrently with primary immunization. This phenomenon was limited to ammonium tetrachloroplatinate II, ammonium hexachloroplatinate IV and to a lesser extent the cesium trichloronitroplatinate II. Platinum group metal salts not possessing this characteristic were cis-dichlorodiammine plantinum II, tetra-ammineplatinum II chloride, ammonium aquopentachlororhodate III and ammonium tetrachloropalladate II. Kinetic studies show that the time courses of the primary and secondary responses were not altered in the presence of the platinum salts. In rats immunized with ovalbumin without adjuvant there was no detectable antibody and concurrent administration of platinum salts also had no effects. Thus platinum salts whilst acting synergistically with adjuvant to enhance antibody synthesis do not act as adjuvants in their own right.

Adjuvants, Immunologic↗
PubMed1994

Characterization of new inbred strains of Dahl-Iwai salt-sensitive and salt-resistant rats.

Dahl-Iwai salt-sensitive (S) and salt-resistant (R) rat strains were newly established as inbred strains. To characterize the strains, the Dahl-Iwai S and R rats were fed low-salt (0.3% NaCl) and high-salt (8.0% NaCl) diets from 5 weeks after birth, and systolic blood pressure and pathologic findings were examined at intervals. The distributions of alleles at 19 biochemical and immunologic loci also were examined in the aforementioned strains, together with those for the inbred SS/Sea and SR/Sea strains, which were derived from inbred SS/Jr and SR/Jr strains, respectively. The Dahl-Iwai S rats were hypertensive after 3 weeks of consuming the 8.0% NaCl diet and died from 6 to 10 weeks after the diet was initiated. Renal lesions developed after 4 weeks' consumption of the high-salt diet. The Dahl-Iwai S rats were not hypertensive until at least the age of 21 weeks while they consumed the 0.3% NaCl diet, whereas it was reported that the SS/Jr rats became hypertensive at about 20 weeks of age when they consumed the low-salt diet. The Dahl-Iwai R rats were normotensive whether fed the 0.3 or 8.0% NaCl diet. Hydronephrosis was not observed in the Dahl-Iwai R rats, though it develops in SR/Jr rats with high frequency. Different distributions were detected for kidney alkaline phosphatase-1 (Akp-1) and amylase-1 (Amy-1) alleles between the Dahl-Iwai S and SS/Sea strains, and for esterase-14 (Es-14) and seminal vesicle protein-1 (Svp-1) alleles between the Dahl-Iwai R and SR/Sea strains. The phenotypic differences between the substrains of inbred Dahl rats could be ascribed to different genetic backgrounds.

Aging↗
PubMed2005

Synthesis of phospholipid-conjugated bile salts and interaction of bile salt-coated liposomes with cultured hepatocytes.

To examine the possibility of targeting liposomes to hepatocytes via bile salts, the bile salt lithocholyltaurine was covalently linked to a phospholipid. The isomeric compounds disodium 3alpha-(2-(1,2-O-distearoyl-sn-glycero-3-phospho-2'-ethanolamidosuccinyloxy)ethoxy)-5beta-cholan-24-oyl-2'-aminoethansulfonate and disodium 3beta-(2-(1,2-O-distearoyl-sn-glycero-3-phospho-2'-ethanolamidosuccinyloxy)ethoxy-5beta-cholan-24-oyl-2'-aminoethansulfonate (DSPE-3beta-LCT) were synthesized and incorporated into liposomal membranes. Confocal laser scanning microscopy studies showed that bile salt-bearing liposomes (BSLs) attach to the surface of rat hepatocytes in culture. Studies with radioactively labeled liposomes revealed that the bile salt linked via the 3beta-conformation resulted in a higher attachment efficiency than that with the 3alpha-derivative. In the presence of BSLs corresponding to 2 mM liposomal phosphatidylcholine, uptake of 50 microM cholyltaurine (CT) into hepatocytes was reduced by approximately 40% by the 3beta-derivative and by approximately 17% by the 3alpha-derivative. When added simultaneously with the liposomes, CT up to 75 microM inhibited the binding of DSPE-3beta-LCT-bearing liposomes. By contrast, increasing concentrations reversed this inhibition and resulted in an increased bile salt-mediated binding. The same was true when CT was added 10 min before the liposomes were added. The attachment of BSLs to the surface of hepatocytes opens up promising possibilities for hepatocyte-specific drug delivery. More generally, not only substrates for cellular endocytosing receptors but also substrates for cellular carrier proteins should be suitable ligands for the cell-specific targeting of nanoscale particles such as liposomes.

Animals↗
PubMed2006

Atp8b1 deficiency in mice reduces resistance of the canalicular membrane to hydrophobic bile salts and impairs bile salt transport.

Progressive familial intrahepatic cholestasis type 1 (PFIC1, Byler disease, OMIM 211600) is a severe inherited liver disease caused by mutations in ATP8B1. ATP8B1 is a member of the type 4 subfamily of P-type ATPases, which are phospholipid flippases. PFIC1 patients generally develop end-stage liver disease before the second decade of life. The disease is characterized by impaired biliary bile salt excretion, but the mechanism whereby impaired ATP8B1 function results in cholestasis is unclear. In a mouse model for PFIC1, we observed decreased resistance of the hepatocanalicular membrane to hydrophobic bile salts as evidenced by enhanced biliary recovery of phosphatidylserine, cholesterol, and ectoenzymes. In liver specimens from PFIC1 patients, but not in those from control subjects, ectoenzyme expression at the canalicular membrane was markedly deficient. In isolated mouse livers Atp8b1 deficiency impaired the transport of hydrophobic bile salts into bile. In conclusion, our study shows that Atp8b1 deficiency causes loss of canalicular phospholipid membrane asymmetry that in turn renders the canalicular membrane less resistant toward hydrophobic bile salts. The loss of phospholipid asymmetry may subsequently impair bile salt transport and cause cholestasis.

Adenosine Triphosphatases↗