The present study investigated the interaction between sodium loading and enalapril on renin synthesis and secretion in hydronephrotic mice. Four different experimental groups (n=10 each) were used: sham-operated animals with normal diet (control group); sodium loading (SL group); enalapril treatment with normal diet (E group), and sodium loading combined with enalapril treatment (SL+E group). The hydronephrotic left kidney was induced by unilateral ureteral ligation in mice in the latter three groups. Plasma renin concentration (PRC) in the aorta, both the left and right renal veins, tissue renin concentration (TRC) and renin mRNA levels in the kidneys were examined under different procedures. In hydronephrotic mice treated with sodium loading, PRC in the left and right renal veins was lower than that in control mice (P<0.05), and TRC and renin mRNA levels in the hydronephrotic kidney were also suppressed (P<0.05). In hydronephrotic mice treated with enalapril, there were significant increases in PRC, TRC and renin mRNA levels in the hydronephrotic and right kidneys compared to the normal control (P<0.01). In hydronephrotic animals treated with sodium loading and enalapril, the increasing response was attenuated, and PRC in the hydronephrotic vein was similar to the level in the aorta. There was an interaction between sodium loading and enalapril on renin-angiotensin system (RAS) in both hydronephrotic and normal kidneys. The mechanism in control of renin synthesis is independent of the macula densa, but the latter is critical in the control of renin secretion.
Animals ; Aorta ; metabolism ; Enalapril ; pharmacology ; Hydronephrosis ; metabolism ; Kidney ; physiopathology ; Mice ; Mice, Inbred BALB C ; RNA, Messenger ; metabolism ; Renin ; metabolism ; Renin-Angiotensin System ; drug effects ; Sodium ; metabolism

OBJECTIVETo review the advances of studies on vitamin D receptor and its role in the pathogenesis of diabetic nephropathy.

DATA SOURCESA comprehensive search of the PubMed literatures without restriction on the publication date was carried out using keywords such as vitamin D receptor and diabetic nephropathy.

STUDY SELECTIONArticles related to vitamin D receptor and diabetic nephropathy were selected and carefully analyzed.

RESULTSThe ligands as well as construction and tissue distribution of vitamin D receptor were summarized. Pathogenesis of diabetic nephropathy was analyzed. The mechanisms underlying the renoprotective role of vitamin D receptor including inhibition of renin-angiotensin system, anti-inflammation, anti-fibrosis and the reduction of proteinuria were reviewed. Mounting evidences from animal and clinical studies have suggested that vitamin D therapy has beneficial effects on the renal systems and the underlying renoprotective mechanisms of the vitamin D receptor-mediated signaling pathways is a hot research topic.

CONCLUSIONOur study suggests that vitamin D receptor has a great potential for preventing the progression of diabetic nephropathy via multiple mechanisms.

Animals ; Diabetic Nephropathies ; metabolism ; Humans ; Proteinuria ; metabolism ; Receptors, Calcitriol ; metabolism ; Renin-Angiotensin System ; physiology

Angiotensinogen ; metabolism ; Animals ; Liver Cirrhosis, Experimental ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley ; Renin-Angiotensin System

The present study was aimed at investigating the regulation of atrial natriuretic peptide (ANP) system in association with either enhanced or attenuated activity of the renin-angiotensin system (RAS). The cardiac tissue mRNA and peptide levels of ANP were measured in rats with two-kidney, one clip (2K1C) or deoxycorticosterone acetate (DOCA)-salt hypertension. Plasma renin concentration was increased in 2K1C hypertension along with increases of renin mRNA and protein contents in the clipped kidney. On the contrary, it was suppressed in DOCA-salt hypertension along with decreases of renin mRNA and protein contents in the remaining kidney. The plasma ANP concentration was similarly increased in both models of hypertension. The cardiac tissue ANP contents were not significantly changed, but the tissue ANP mRNA levels were upregulated in the hypertrophied heart in these two models of hypertension. It is suggested that the cardiac ANP system is transcriptionally enhanced by cardiac hypertrophy associated with hypertension, independent of the systemic RAS.
Animal ; Atrial Natriuretic Factor/metabolism* ; Desoxycorticosterone ; Gene Expression Regulation ; Hypertension/metabolism* ; Hypertension/chemically induced ; Male ; Myocardium/pathology ; Organ Weight ; Peptides ; RNA, Messenger/analysis ; Rats ; Rats, Sprague-Dawley ; Renin/genetics* ; Renin/blood* ; Renin-Angiotensin System/physiology

Even though we drink and excrete water without recognition, the amount and the composition of body fluid remain constant everyday. Maintenance of a normal osmolality is under the control of water balance which is regulated by vasopressin despite sodium concentration is the dominant determinant of plasma osmolality. The increased plasma osmolality (hypernatremia) can be normalized by the concentration of urine, which is the other way of gaining free water than drinking water, while the low plasma osmolality (hyponatremia) can be normalized by the dilution of urine which is the only regulated way of free water excretion. On the other hand, volume status depends on the control of sodium balance which is regulated mainly by renin-angiotensin-aldosterone system, through which volume depletion can be restored by enhancing sodium retention and concomitant water reabsorption. This review focuses on the urine concentration and dilution mechanism mediated by vasopressin and the associated disorders; diabetes insipidus and syndrome of inappropriate antidiuretic hormone secretion.
Body Fluids ; Diabetes Insipidus ; Drinking Water ; Hand ; Metabolism* ; Osmolar Concentration ; Plasma ; Renin-Angiotensin System ; Sodium ; Vasopressins

OBJECTIVETo explore the time course of renin-angiotensin system (RAS), peroxisome proliferator-activated receptor (PPAR) alpha and PPARgamma change in an animal model of alcoholic cardiomyopathy (ACM).

METHODSAdult rats were divided into three groups: ACM group (A, 10% alcohol as drinking water plus 5 ml 60% alcohol.kg(-1).d(-1) per gavage in the 1st week; 10% alcohol as drinking water plus 10 ml 60% alcohol/kg bid per gavage in the 2nd week, 20% alcohol as drinking water plus 15 ml 60% alcohol/kg bid per gavage during week 3 to week 16), ACM/ARB group(B, A + Irbesartan 5 mg.kg(-1).d(-1) per gavage) and control group (C). mRNA expressions and activities of renin, angiotensin, ACE and AT1 were detected with RT-PCR and radioimmunoassay methods. Protein expressions of PPARalpha and PPARgamma were determined with Western blot. Echocardiogram, optic (HE) and electron microscope examinations were also performed. Parameters were obtained at 2 or 6 months (n = 7 - 10 each).

RESULTSCompared with group C, LV/BW ratio was significantly increased and LVEF significantly decreased, activities and expressions of Ang I, Ang II and renin were gradually increased, protein expressions of PPARalpha were gradually decreased at 2 and 6 months in group A (all P < 0.05). These changes could be partly attenuated by Irbesartan.

CONCLUSIONActivated RAS and decreased protein expressions of PPARalpha and PPARgamma contributed to the development of ACM.

Animals ; Cardiomyopathy, Alcoholic ; metabolism ; Disease Models, Animal ; Male ; PPAR alpha ; metabolism ; PPAR gamma ; metabolism ; Rats ; Rats, Wistar ; Renin-Angiotensin System

Hepatitis B, Chronic ; metabolism ; Humans ; Liver Cirrhosis ; metabolism ; RNA, Messenger ; analysis ; Receptor, Angiotensin, Type 1 ; genetics ; Renin ; genetics

Osteopontin (OPN) is a secreted phosphoprotein that is constitutively expressed in the normal kidney and is induced by various experimental and pathologic conditions. Several possible functions of OPN have been suggested, however the mechanism and significance of OPN expression are still uncertain. Since high salt concentration or salt crystal have been known to enhance OPN expression in intact kidney or cultured renal cells, in the present study we examined whether or not a low salt condition had an effect on OPN expression in the kidney. Adult male Sprague-Dawley rats were fed either a normal sodium or a sodium deficient diet for 1 week. Kidneys were processed for in situ hybridization using a digoxigenin-labeled riboprobe and for immunohistochemistry using antibodies to OPN, renin, and Na-K-ATPase. In rats fed a normal sodium diet, OPN mRNA and protein were expressed only in the descending thin limbs of Henle's loop (DTL) and in the papillary and pelvic surface epithelium (PSE). In rats fed a sodium deficient diet, there was a marked decrease in OPN immunoreactivity in the DTL, but no changes in PSE. In contrast, no changes were observed in OPN mRNA expression in the DTL by in situ hybridization, indicating that decreased OPN protein expression was a result of translational regulation. As expected, rats fed a sodium deficient diet were associated with increased immunoreactivity for Na-K-ATPase and renin compatible with activation of the renin-angiotensin system. These results suggest that dietary sodium may be involved in the regulation of OPN expression in the DTL of the rat kidney.
Animal ; Diet, Sodium-Restricted* ; Immunohistochemistry ; In Situ Hybridization ; Kidney/metabolism* ; Male ; Na(+)-K(+)-Exchanging ATPase/metabolism ; Rats ; Rats, Sprague-Dawley ; Renin/metabolism ; Sialoglycoproteins/metabolism ; Sialoglycoproteins/antagonists & inhibitors* ; Sodium/deficiency*

This study investigated the anti-ascites effect of the total saponins of Phytolaccae Radix(PRTS) and the mechanism.H22 cell suspension was used(ip) to induce ascites in ICR male mice, and the model mice were randomized into model group, positive drug group(furosemide, 6 mg·kg~(-1)), total extract of Phytolaccae Radix(PRTE) group, and PRTS(1.29 g·kg~(-1)).Another 10 male mice were selected as the blank group.Mice in the blank group and model group were given(ig) normal saline containing 0.5% CMC-Na, and those in the positive drug group, PRTE group, and PRTS group received(ig) corresponding doses of drugs, once a day, for 8 consecutive days.The ascites volume, urine volume, and fecal water content in mice with ascites, serum levels of antidiure-tic hormone(ADH), renin in renin-angiotensin-aldosterone system(RAAS), angiotensin Ⅱ(AngⅡ), and aldosterone(ALD), expression of aquaporin(AQP)1-AQP4 in kidney, expression of AQP1, AQP3 in colon, and expression of phosphatidylinositol 3-kinase/protein kinase B(PI3 K/Akt) pathway-related proteins were detected to explore the anti-ascites mechanism of PRTS.The results showed that the PRTS can increase the urine volume and fecal water content and decrease the ascites volume of ascites mice.Moreover, PRTS significantly reduced the expression of AQP1-AQP4 in kidney and AQP1, AQP3 in colon, serum levels of renin, AngⅡ, ALD, and ADH, and the expression of p-PI3 K and p-Akt in the kidney of ascites mice.PRTS exerts anti-ascites effect by promoting urination and defecation.The mechanism is that it inhibits the activities of RAAS and ADH and suppresses the phosphorylation of PI3 K/Akt signaling pathway, thereby restricting the expression of AQPs in the kidney and colon.
Animals ; Aquaporin 1 ; Ascites/metabolism* ; Male ; Mice ; Mice, Inbred ICR ; Proto-Oncogene Proteins c-akt/metabolism* ; Renin/metabolism* ; Saponins/pharmacology* ; Water/metabolism*

Patients suffering from idiopathic or self-induced edema are uniformly characterized by chronic use of furosemide, which leads to vicious cycle of edema. Among chronic furosemide users who don't have any other specific edema forming diseases, 9 patients from the outpatient clinic(OC) and 6 patients examined at the emergency room(ER) used it mainly for weight reduction and for cyclical edema, respectively. All of the ER group patients were presented with severe hypokalemia(2.04+/-0.2mEq/L; range 1.3 to 2.7 mEq/L) and alkalosis(748+/-0.01; range 7.44 to 7.51) but none from the OC group showed such results. Other baseline parameters including Plasma renin activity(PRA) and aldosterone level on recumbency, and FEn(2)were similar in both groups. In contrast, daily working hours(6.1+/-0.5 vs 10+/-0.6hr, p<0.01), average body weight gain between AM and PM(0.4+/-0.1 vs 0.9+/-0.lkg, p<0.01), peak weight gain interval(9+/-0.8 vs 5+/-0.1day, p<0.05), PRA(7.6+/-1.5 vs 23.5+/-7.2ng/ml/h, p<0.05) and aldosterone level(22.1+/-4.2 vs 64.8+/-10.4 ng/dl, p<0.01) on ambulation, and FEk. on normokalemia(ll+/-2A vs 36+/-7.7%, p<0.01) were statistically different between the two groups. In comparison to the OC group, both the amout of urine(617+/-39 vs 358+/-26ml, p<0.01) and the percent change of PRA(-14+/-4 vs -3+/-2%, p<0.05) and al-dosterone level(-17+/-5 vs -4+/-3%, p<0.05) after saline loading(lL over 1hr, IV) following ambulation were smaller in the Elt group. Moat of the ER group patients(5/6) required aldosterone antagonist (spironolactone) added to K+ supplement, but all of the OC group patients were managed to maintain an edema-free status with conservative treatment. In conclusion, patients with idiopathic edema seem to have more fluid transudation out of intravascular space during orthostasis with a prominent degree of deranged renin-aldosterone axis and K+ metabolism than those with self-induced edema.
Aldosterone ; Axis, Cervical Vertebra ; Body Weight ; Dizziness ; Edema* ; Emergencies ; Furosemide* ; Humans ; Metabolism ; Outpatients ; Plasma ; Renin ; Walking ; Weight Gain ; Weight Loss