Las hormonas femeninas en fisiología renal: Sensibilidad a la sal y regulación de la proliferación epitelial / Female hormones in renal physiology. Salt sensitivity and regulation of epithelial proliferation

Un tercio de la población mundial tiene niveles anormalmente altos de presión arterial, hipertensión, responsable de casi el 50% de las muertes por accidente cerebrovascular y enfermedad coronaria. La sensibilidad a la sal es un factor de riesgo para la morbilidad y mortalidad cardiovascular y también para otras enfermedades. En estudios previos describimos un modelo de hipertensión sal sensible (HSS) en ratas Wistar ovariectomizadas (oVx) adultas. Las ratas oVx son normotensas con ingesta normal de sal (NS, 0.24% de NaCl), pero desarrollan un perfil de HSS con una ingesta elevada de sal (HS, 1% de NaCl). En los estudios en riñón encontramos que el circuito receptor D1 de dopamina, citocromo P450 4A y Na+, K+-ATPasa está alterado por la ausencia de hormonas ováricas, lo que se asocia a menor excreción de sodio e hipertensión arterial. La ingesta HS en ratas oVx también promueve cambios en la expresión de proteínas relacionadas con el transporte de sodio en células mononucleares de sangre periférica, principalmente linfocitos periféricos. Por lo tanto, el transporte de sodio se modifica en varios niveles de la fisiología normal. En estudios recientes observamos que el estradiol aumenta la proliferación y diferenciación de células epiteliales en cultivos de corteza renal humana. Sensibilidad a la sal, inmunidad adaptativa, presión arterial y proliferación de células epiteliales en riñón son fenómenos de gran importancia biológica regulados por estradiol.

Female sex hormones participate in the regulation of blood pressure and renal epithelial proliferation, effects not related to their reproductive function. About one-third of the world's population has abnormally high levels of blood pressure, hypertension, which is responsible for almost 50% of deaths from stroke and coronary heart disease. Salt sensitivity is a risk factor for cardiovascular morbidity and mortality and other diseases as well. We reported a model of salt sensitive hypertension in adult ovariectomized (oVx) Wistar rats. oVx rats are normotensive under normal salt intake (NS, 0.24% NaCl), but upon a high salt intake (HS, 1% NaCl) oVx rats developed a blood pressure profile of salt-sensitive hypertension. Our studies on kidney molecules related to sodium balance found that the circuit dopamine D1-like receptor, cytochrome P450 4A and Na+, K+-ATPase is altered by the absence of ovary hormones which is accompanied by a reduced ability to excrete sodium. In oVx rats HS intake also promotes changes in the expression of proteins related to sodium transport in peripheral blood mononuclear cells, mainly peripheral lymphocytes. Therefore, sodium transport is modified at several levels of normal physiology. Lately, we described that estradiol increases the rate of renal epithelial cell proliferation in primary cultures developed from human renal cortex. Thus, salt sensitivity, adaptive immunity, blood pressure and renal cell proliferation are complex biological responses regulated by female sex hormones.

Effects of Sodium Intake on the Association between the Salt-Sensitive Gene, Alpha-Adducin 1 (ADD1), and Inflammatory Cytokines in the Prevalence of Children Obesity

OBJECTIVE: To examine the effects of sodium intake on the correlations between the salt-sensitive gene α-adducin 1 (ADD1) and inflammatory cytokines in Korean childhood obesity. METHODS: A total of 2,070 students aged 8–9 years old participated in this study. The anthropometrics, serum biochemistry profile, inflammatory cytokines, and three-day dietary assessment were analyzed according to sex, obesity degree, and ADD1 polymorphism. RESULTS: The obesity prevalence was higher in boys (15.6%) than in girls (11.9%). Boys also showed higher values in anthropometrics; lipid, glucose, and insulin profiles; total calorie intakes, as well as those of sodium and calcium compared with those of the girls. The more obese were boys and girls, the higher were the anthropometrics and the blood levels (total cholesterol, triglyceride, low-density lipoprotein cholesterol, fasting blood sugar, and insulin), but the lower was high-density lipoprotein cholesterol. The obese boys had significantly higher sodium and Na/K intakes, while the obese girls had higher visfatin level and Na/K intake. In addition, an increase in the risk factors for blood pressure and obesity in ADD1 variants was identified. Serum tumor necrosis factor-α(TNF-α) significantly increased with increasing sodium intake in the ADD1 W allele carriers, regardless of sex. The presence of obesity with the ADD1 W allele induced inflammatory accelerators such as TNF-α or C-reactive protein(CRP) with higher sodium intake. CONCLUSION: Obese children with an ADD1w allele can experience a more complex form of obesity than non-obese when exposed to an obesity-inducing environment and need to be controlled sodium intake in the diet.

Study on the mechanism of PSGL-1 in salt-sensitive hypertension via inflammation in mice / 中国比较医学杂志

Objective To investigate the role and mechanism of PSGL-1 in development of salt-sensitive hypertension in mice. Methods PSGL-1 knockout(PSGL-1 -/-)and wild type(PSGL-1 +/ +)mice were fed a high salt (6% NaCl)or normal salt(0.4% NaCl)diet for three months. Blood pressure was measured under anesthesia via the carotid artery. The status of tissue inflammation and kidney injury was tested by flow cytometry, immunohistochemistry, and western blotting. Results Compared with mice fed a normal salt diet, PSGL-1 +/ +mice fed a high salt diet for three months showed high blood pressure, increased inflammatory cell infiltration in the aorta and skin, and increased inflammatory cytokine expression(interleukin-6, interleukin-1β, and tumor necrosis factor-α)in the kidney, as well as elevated expression of the kidney injury marker, connective tissue growth factor. In contrast, inflammation and kidney injury were not found in PSGL-1 -/-mice fed a high-salt diet. Conclusions In mice,PSGL-1 via inflammation plays a key role in development of hypertension and kidney injury caused by high salt intake.

Influence of Different Dietary Salt Concentration on the Renal Fibrosis and Macrophages Infiltration in Salt Sensitive Hypertension / 现代生物医学进展

Objective:To investigate the influence of different salt concentration on the renal fibrosis and macrophages infiltration in salt sensitive hypertension.Methods:Dahl salt sensitive rats were randomly divided into the normal salt (0.3 ％ nacl) group,4 ％ high salt,8 ％ high salt groups at six weeks continuously feeding for 8 weeks,each group contained 15 rats.Tail-cuffmethod was used to value rat blood pressure at 8 weeks,Masson trichromatic method was used to detect renal fibrosis of the three groups at 8 week.Immunohistochemistry and Western blot method were used to depict the renal macrophage infiltration at 8 week.Results:1) The blood pressure of 4 ％ salt and 8％ high salt group rats were significantly higher than those of the normal salt group at 8week,meanwhile the blood pressure of 8 ％ high salt was further increased than that of 4 ％ high salt group at 8 week.2) The relative kidney weight and renal fibrosis of 4 ％ salt and 8 ％ high salt group rats were obviously higher than that of normal salt group at 8week,meanwhile the relative kidney weight and renal fibrosis of 8 ％ high salt were further increased than those of 4 ％ high salt group at 8 week.3) The macrophage infiltration of 4 ％ salt and 8％ high salt group rats were higher than that of the normal salt group at 8week,meanwhile the macrophage infiltration of 8 ％ high salt was further increased than that of 4 ％ high salt group at 8 week.Conclusion:Different high salt concentrations had different effect on the renal fibrosis and macrophage infiltration in the salt sensitive hypertension,high salt concentration could exacerbate the renal fibrosis and macrophage infiltration.

Clinical Study of Androgen Receptor (CAG) Gene Polymorphism and Androgen in Male with Salt Sensitive Hypertension / 现代检验医学杂志

Objective To investigate the relationship between androgen receptor CAG-gene polymorphism and androgen in male with salt sensitive hypertension.Methods Through the oral saline loading test and furosemide volume method male hypertension group were divided into salt-sensitive (SS group) and salt-insensitive (SR group).The samples from 161 males were selected in the study,including salt sensitive hypertension patients (SS group,61/161),salt-insensitive hypertension patients (SR group,40/161) and age-matched healthy samples (control group,60/161).All samples were sequenced with an analysis method (CAG) n repeated polymorphism,and determinated of total testosterone (TT) and free testosterone (FT) level in serum by electrochemiluminescence immunoassay.Results The number of CAG repeats was 14～34,average 22.4± 2.7.The CAG repeats of SS,SR and control group were 23.5±3.75,22.3±3.17 and 21.8±2.95,respectively.There were significant differences among the three groups (t=2.627～ 3.257,all P＜0.05).The level of TT and FT in SS and SR group were decreased compared with that of control group.At the same time,the level of SS group was lower,and there were significant differences among the three groups (t=2.524～ 3.826,all P＜0.05).Conclusion The androgen receptor gene repeat length and androgen levels are associated with male hypertension,especially salt-sensitive hypertension.Long (CAG) n repeat polymorphism maybe a genetic factor in the pathogenesis of hypertension.Plasma androgen levels may be used as a predictor of male salt sensitive hypertension.

Effect of Electroacupuncture on Renal CaM/NO Pathway in Dahl Rats with Prehypertension / 上海针灸杂志

Objective To investigate the effect of electroacupuncture on renal CaM-eNOS-NO signal pathway in Dahl salt-sensitive rats with prehypertension.Methods Thirty 7-week-old male Dahl salt-sensitive rats (DS) were allocated,using a random number table,to model,acupuncture and non-meridian-acupoint groups.Ten 7-week-old male Dahl salt-resistant rats (DR) were used as a blank group.The rats were fed in a SPF animal experiment center.An 8％ NaC1 high salt diet was provided after 1-week adaptive feeding.During the period,rat blood pressure was monitored using an intelligent noninvasive sphygmomanometer.A rat model of prehypertension was successfully made if rat blood pressure rose to 120～ 139/80～89 mmHg after 12 days.At that time,a high salt diet was stopped and a normal diet was provided.The blank and model groups received 15-minute regular fixation and no treatment.The acupuncture group received electroacupuncture at bilateral Quchi and Zusanli.The non-meridianacupoint group received electroacupuncture at fixed control points selected between 10 and 15 mm above bilateral iliac crests 20 mm lateral to the midline.Treatment was given once daily,6 times a week,for five consecutive weeks.The left rat kidney was taken.CaM and eNOS mRNA expressions were determined by quantitative fluorescence PCR.eNOS was quantified and located by western blot and immunohistochemical method.NO content was measured by ELISA.Results As compared with the blank group,CaM and eNOS mRNA expressions,eNOS protein content and NO content decreased significantly in the model group (all P＜0.05).As compared with the model group,CaM and eNOS mRNA expressions,eNOS protein content and NO content increased significantly in the acupuncture group (all P＜0.05).As compared with the model group,CaM expression increased significantly (P＜0.05) but eNOS mRNA expression and NO content had no statistically significant differences (P＞0.05) in the non-meridian-acupoint group.Conclusion The renoprotective effect of electroacupuncture at Quchi and Zusanli may be related to upregulating renal CaM-eNOS-NO signal pathway in DS rats with prehypertension.

The study on the mechanism of platelet in the development of salt-sensitive hypertension via inflammation / 中国比较医学杂志

Objective To investigate the role and mechanism of platelet in the development of salt-sensitive hypertension.Methods 25 Dahl salt-sensitive rats (Dahl SS) were divided into three groups: low-salt diet (0.12% NaCl, LS), high-salt diet (8%NaCl, HS) and high-salt diet + platelet inhibitor (8%NaCl+busulfan, HS+bus).Blood pressures were measured by tail-cuff method.After six weeks, animals were sacrificed.Platelet p-selectin expression, platelet cytosolic Ca2+ concentration, platelet-leukocyte aggregation (PLA) in peripheral blood, and immune cells infiltrated on aortic walls were assessed by flow cytometry, and serum IL-6 level was tested by ELISA in vivo.Platelets purified from SD rats were treated with normal salt (0.9%NaCl) and high salt (1.3%NaCl), then the cytosolic Ca2+ concentration and p-selectin expression of platelet were detected.Results We found that Dahl SS rats with high-salt diet, relative to low-salt diet, presented with high blood pressure and increased the ratio of platelet p-selectin expression, Ca2+ concentration.IL-6 level and PLA in peripheral blood, and the number of infiltrated immune cells on aortic walls were also significantly elevated in high-salt diet group.The whole events were ameliorated by the platelet inhibitor busulfan.Cytosolic Ca2+ concentration and p-selectin expression were also increased in purified platelets treated with high salt than those treated with low salt (P < 0.05).Conclusions Our findings suggest that high salt induced platelet activation with increased Ca2+ concentration may play an important role in the development of salt-sensitive hypertension via vascular inflammation.However, the detailed mechanisms of platelet activation and development of high blood pressure via inflammation induced by high salt intake remain to be determined.

Effects of interaction between SLC12A3 polymorphism, salt-sensitive gene, and sodium intake on risk of child obesity / 한국영양학회지

PURPOSE: Obesogenic environments in children, in particular excessive intake of sodium, generate hypertension, which is a major risk factor for chronic diseases. METHODS: In all, 725 children, 379 boys and 373 girls, aged 8∼9 years were recruited from seven elementary schools in Kuro-ku, Seoul. To evaluate whether or not obesity risk was modulated by salt-sensitive genes, Solute Carrier Familiy 12 member 3 (SLC12A3) was used as the target. After children were assigned into obese (BMI > 85 percentile) or non-obese groups, anthropometry, blood biochemistry, and dietary intakes were measured according to the genotypes GG (wild) or GA+AA (hetero+mutant). RESULTS: Without gender differences, high TG and low HDLc were detected in the obese group compared to the non-obese group. Regardless of obesity, weight gain and blood pressure (BP) increased in the SLC12A3 GA+AA genotype rather than in the GG type. HDLc was associated with obesity risk without genotype difference. Odd ratios for risk of obesity were 15.57 (95% CI 2.192∼110.654), 22.84 (95% CI 1.565∼333.469), and 9.32 (95%CI 1.262∼68.817) in boys and girls with GA+AA genotypes as sodium intake increased above 4,000 mg/day. Dietary calcium, sodium, folate, and vit C were associated with obesity risk according to gender or genotype differences. Since high folate intake reduced obesity risk in only boys with GG type. Risk for overweight and obesity increased in boys with GA+AA genotypes and dietary habits with high sodium and cholesterol and low folate. CONCLUSION: The A allele of SLC12A3 rs11643718 was sensitive to development of obesity in children as sodium intake increased.

CURATIVE EFFECT OF COMBINATION OF DRUGS IN THE TREATMENT OF SALT-SEN-SITIVE HYPERTENSION / 现代医院

Objective To discuss the clinical effect and influence combination of drugs on the functions of target organs in the patients with salt-sensitive hypertension.Methods 125 patients with salt-sensitive hypertension, their clinical data retrospec-tively analyzed, divided into two groups, treated with coaprovel and felodipine combined with irbesartan respectively for 8 weeks.The levels of left ventricular mass index (LVMI), fasting blood glucose (FBG), triglyceride (TC), total cholesterol (TC) and blood 2-microglobulin (2-MG) during the treatment were then observed.Results The amplitude of blood pressure was significantly lower in the coaprovel group after 4 weeks and 8 weeks of treatment in the patients with salt -sensitive hypertension.However, there was no statistical difference of effectiveness between the coaprovel group ( 81.0%) and the felodipine combined with irbesartan group (83.9%).The decrease range of LVMI showed significantly better results in the coaprovel group (28.9 ±7.3).Moreover, there was no statistical difference in other indexes between two groups or before and after treatment .Conclusion Coaprovel has a similar cura-tive effect with felodipine combined with irbesartan in the treatment of patients with salt -sensitive hypertension.It has more signifi-cant protective effect for heart damage .

Papel de la inflamación renal en la fisiopatología de la hipertensión sensible a sal / Role of renal inflammation in the physiopathology of salt-sensitive hypertension

La hipertensión sensible a sal es el aumento de la presión arterial luego de una sobrecarga salina, como consecuencia esencialmente de una disminución en la excreción renal de sodio. En los últimos años, ha sido desarrollada una teoría para explicar su origen que tiene como base la inflamación del tejido renal. El proceso inicia con la producción en los riñones de radicales libres derivados del metabolismo oxidativo. Luego se desarrolla un mecanismo de inflamación del intersticio renal por infiltración de linfocitos T, y otras células inmunológicas. Fundamentalmente los linfocitos T incrementan la producción de angiotensina II que estimula la retención de sodio y agua a este nivel, favoreciendo el desarrollo de hipertensión sensible a sal. La relación entre infiltración renal por células del sistema inmune e hipertensión sensible a sal permite, en parte, explicar la asociación entre enfermedades autoinmunes y la hipertensión arterial. El uso de antioxidantes y el diseño de nuevos fármacos pueden ser una alternativa adicional al tratamiento de los pacientes afectados.

Salt-sensitive hypertension is produced by a decrease in salt renal excretion after a salt overload. Over the last few years, a new theory has been developed to explain this condition based on renal tissue inflammation. This process begins with free radicals production in renal tissue due to oxidative metabolism. Then they favor a renal inflammation mechanism with T-lymphocytes infiltration and other immune cells. Essentially, T-lymphocytes determine an increase in angiotensin II production which raises sodium and water retention. Association among autoimmune diseases and hypertension may be explained, in part, by the relationship between salt-sensitive hypertension and renal inflammation. The use of antioxidant drugs and the development of new medicaments may be a choice for treating patients affected with this condition.

Regulation of nitrogen metabolism in salt tolerant and salt sensitive Frankia strains.

Effect of salinity (0, 50, 100, 250, 500 and 750 mM NaCl) was observed on some important physiological parameters of nitrogen metabolism such as nitrate uptake, intracellular and extracellular ammonium status and activities of nitrogenase, nitrate reductase, nitrite reductase and glutamine synthetase among Frankia strains differing in their salt tolerance capacity. Nitrogenase activity closely followed the growth pattern with regular decline on NaCl supplementation. All the other enzymes showed optimum activity at 100 mM and declined further. Co-regulation of the nitrate uptake system and sequential enzyme activities plays a crucial role in governing the nitrogen status of strains during salt stress. HsIi10 experiencing minimum decline in enzyme activities and best possible nitrogen regulation under NaCl replete condition showed adequate nutritional management. Among all the strains, HsIi10 proved to be salt tolerant on account of above features while the salt sensitive strain HsIi8 lacked the ability to regulate various steps of nitrogen metabolism during salinity, and thus Frankia strain HsIi10 can potentially serve as a potential biofertilizer in the saline soil.

Salt-induced epithelial-to-mesenchymal transition in Dahl salt-sensitive rats is dependent on elevated blood pressure

Dietary salt intake has been linked to hypertension and cardiovascular disease. Accumulating evidence has indicated that salt-sensitive individuals on high salt intake are more likely to develop renal fibrosis. Epithelial-to-mesenchymal transition (EMT) participates in the development and progression of renal fibrosis in humans and animals. The objective of this study was to investigate the impact of a high-salt diet on EMT in Dahl salt-sensitive (SS) rats. Twenty-four male SS and consomic SS-13BN rats were randomized to a normal diet or a high-salt diet. After 4 weeks, systolic blood pressure (SBP) and albuminuria were analyzed, and renal fibrosis was histopathologically evaluated. Tubular EMT was evaluated using immunohistochemistry and real-time PCR with E-cadherin and alpha smooth muscle actin (α-SMA). After 4 weeks, SBP and albuminuria were significantly increased in the SS high-salt group compared with the normal diet group. Dietary salt intake induced renal fibrosis and tubular EMT as identified by reduced expression of E-cadherin and enhanced expression of α-SMA in SS rats. Both blood pressure and renal interstitial fibrosis were negatively correlated with E-cadherin but positively correlated with α-SMA. Salt intake induced tubular EMT and renal injury in SS rats, and this relationship might depend on the increase in blood pressure.

Change of the renal hydrogen sulfide system in salt-sensitive hypertensive rats / 中华实用儿科临床杂志

Objective To study the change of the renal endogenous hydrogen sulfide (H2 S) pathway in the development of salt-sensitive hypertension in Dah1 rats.Methods Sixteen male Dah1 rats,in accordance with the random number table,were randomly divided into control group and high salt group fed with diet containing 80 g/kg NaCl.After 8 weeks,24 h urine sodium,24 h urinary protein,serum creatinine and serum urea were measured.The microstructural and ultrastructural changes in kidney were observed with light microscope and electronic microscope.The serum and kidney H2S contents were determined by using sulphur-sensitive electrode method.The mRNA levels of cystathionine β-synthase(CBS),cystathionine γ-lyase(CSE) and mercaptopyruvate sulfurtransferase(MPST) in renal tissue were determined by means of real-time polymerase chain reaction(RT-PCR).The protein expressions of CBS,CSE and MPST in renal tissue were detected by using Western blot.Results Compared with control group,high salt group rats had a significant rise in blood pressure,declined renal function,damaged renal structure,segmental glomerular sclero sis,small artery wall thickening,and occlusion of the lumen.Moreover,the endogenous H2S pathway in kidney of Dah1rats with high salt diet was downregulated markedly,demonstrated by the decreased serum and kidney H2S content,the reduced renal CBS,CSE and MPST mRNA expressions and CBS protein expression of kidney tissue.Conclusion The endogenous H2S/CBS pathway is downregulated during the development of salt-sensitive hypertension in Dah1 rats.

Partial baroreceptor dysfunction and low plasma nitric oxide bioavailability as determinants of salt-sensitive hypertension: a reverse translational rat study

This study determined whether clinical salt-sensitive hypertension (cSSHT) results from the interaction between partial arterial baroreceptor impairment and a high-sodium (HNa) diet. In three series (S-I, S-II, S-III), mean arterial pressure (MAP) of conscious male Wistar ChR003 rats was measured once before (pdMAP) and twice after either sham (SHM) or bilateral aortic denervation (AD), following 7 days on a low-sodium (LNa) diet (LNaMAP) and then 21 days on a HNa diet (HNaMAP). The roles of plasma nitric oxide bioavailability (pNOB), renal medullary superoxide anion production (RMSAP), and mRNA expression of NAD(P)H oxidase and superoxide dismutase were also assessed. In SHM (n=11) and AD (n=15) groups of S-I, LNaMAP-pdMAP was 10.5±2.1 vs 23±2.1 mmHg (P<0.001), and the salt-sensitivity index (SSi; HNaMAP−LNaMAP) was 6.0±1.9 vs 12.7±1.9 mmHg (P=0.03), respectively. In the SHM group, all rats were normotensive, and 36% were salt sensitive (SSi≥10 mmHg), whereas in the AD group ∼50% showed cSSHT. A 45% reduction in pNOB (P≤0.004) was observed in both groups in dietary transit. RMSAP increased in the AD group on both diets but more so on the HNa diet (S-II, P<0.03) than on the LNa diet (S-III, P<0.04). MAP modeling in rats without a renal hypertensive genotype indicated that the AD*HNa diet interaction (P=0.008) increases the likelihood of developing cSSHT. Translationally, these findings help to explain why subjects with clinical salt-sensitive normotension may transition to cSSHT.

Different combination of drugs regarding the damage on organs targeting salt sensitivity or non-salt-sensitive hypertension / 中华流行病学杂志

Objective To study the damage on organs from salt sensitivity hypertension or non-salt-sensitive hypertension and the selection of drug combination.Methods 120 hypertensive patiems including 60 cases salt-sensitive (SS) and 60 non-salt-sensitive (NSS) groups were selected in our hospital and their salt load tested.These two groups were randomly divided into two groups,each group with 30 patients,one was given felodipine and perindopril and the others were given indapamide sustained release tablets and peridopril to facilitate the 12-week treatment.Before and after the treatment,patients were tested for physiological indicators,such as sitting blood pressure,24-hour ambulatory blood pressure,insulin resistance index,comparing changes of various sub-index etc.Results Significantly different were seen in indices as fasting blood glucose and serum creatinine (P＜ 0.01),fasting insulin,left ventricular mass index,urinary albumin,body mass index,insulin resistance indices,while between the SS group and the NSS group(P＜0.05).In the SS group,when patients with various sub-indicators were using perindopril combined with indapamide treatment,the related detected indicators tended to be normal and with statistically significant differences (P＜0.05).In the NSS group,those related indexes also tended to be more normal when using felodipine combined with perindopril.However,there were statistically significant differences between the two groups (P＜0.05).Conclusion On SS hypertensive patients with target organ damages,perindopril and indapamide seemed to be more effective in NSS patients,indicating that the use of perindopril and felodipine combination,seemed to be more suitable.

Prostaglandin E receptors in regulation of blood pressure / 中国药理学通报

Prostaglandin E_2(PGE_2)is one of the major metabolic products of arachidonic acid.PGE_2 plays important roles in various important physiological processes by binding to its G protein-coupled receptors designated EP1,EP2,EP3,and EP4,respectively.EP receptors are highly expressed in the kidney and cardiovascular system,and PGE2-mediated activation of EP receptors plays important roles in the regulation of blood pressure.The abnormal expression of EP receptors in the kidney and cardiovascular system is associated with some blood pressure disease such as salt-sensitive hypertension,renal hypertension,and myocardial hypertrophy.

Altered Regulation of Renal Sodium Transporters in Salt-Sensitive Hypertensive Rats Induced by Uninephrectomy

Uninephrectomy (uNx) in young rats causes salt-sensitive hypertension (SSH). Alterations of sodium handling in residual nephrons may play a role in the pathogenesis. Therefore, we evaluated the adaptive alterations of renal sodium transporters according to salt intake in uNx-SSH rats. uNx or sham operations were performed in male Sprague-Dawley rats, and normal-salt diet was fed for 4 weeks. Four experimental groups were used: sham-operated rats raised on a high-salt diet for 2 weeks (CHH) or on a low-salt diet for 1 week after 1 week's high-salt diet (CHL) and uNx rats fed on the same diet (NHH, NHL) as the sham-operated rats were fed. Expression of major renal sodium transporters were determined by semiquantitative immunoblotting. Systolic blood pressure was increased in NHH and NHL groups, compared with CHH and CHL, respectively. Protein abundances of Na+/K+/2Cl- cotransporter (NKCC2) and Na+/Cl- cotransporter (NCC) in the CHH group were lower than the CHL group. Expression of epithelial sodium channel (ENaC)-gamma increased in the CHH group. In contrast, expressions of NKCC2 and NCC in the NHH group didn't show any significant alterations, compared to the NHL group. Expressions of ENaC-alpha and ENaC-beta in the NHH group were higher than the CHH group. Adaptive alterations of NKCC2 and NCC to changes of salt intake were different in the uNx group, and changes in ENaC-alpha and ENaC-beta were also different. These altered regulations of sodium transporters may be involved in the pathogenesis of SSH in the uNx rat model.

Interference of valsartan on blood pressure and plasma angiotensin Ⅱ,aldosterone in salt sensitive essential hypertensive patients / 中国临床药理学与治疗学

AIM: To investigate the interference of valsartan on blood pressure and plasma angiotensin Ⅱ (ang Ⅱ), aldosterone (ALD) in salt sensitive essential hypertensive patients. METHODS: Eighty-four adult hypertensive patients were enrolled in study, and the salt sensitivity was determined by acute intravenous salt water loading according to Sullvan's criteria. The change of blood pressure and plasma ang Ⅱ, and ALD were compared before and after the treatment. RESULTS: At the end of 2, 4, 6, and 8 weeks, patients with salt sensitive essential hypertensive (group ss) and no salt sensitive essential hypertensive (group nss) were measured. The results showed that sitting systolic blood pressure (SiSBP) was decreased by 17.5 ? 4.3 and 11.0 ? 1.4 mmHg, and sitting diastolis blood pressure (SiDSP) was decreased by 17.0 ? 3.7 and 7.3 ? 1.1 mmHg after the treatment. It was found that patients showed significantly higher plasma ang Ⅱ and lower plasma ALD in group ss and group nss. CONCLUSION: Valsartan can significantly control SiSBP and SiDBP for both groups, interfered plasma angiotensin Ⅱ and I aldosterone, and be more effective for patients with salt sensitive essential hypertensive.

The Effet of Nifedipine on the Blood Pressure, Water and Cation Balance of the Lens in Spontaneous Hypertensive Rats

In systemic hypertension, capillary resistance is highly elevated and' contractility of vascular smooth muscle is elevated. This is due to increased calcium uptake into the sarcoplasmic reticulum of the vascular smooth muscle. Recently, nifedipine, an antihypertensive medication which inhibits calcium uptake into the vascular smooth muscle is commonly used. It decreases the contractility of the vascular smooth muscle and causes the vessels to relax, which in turn lowers the blood pressure. In 1987, according to Rodriguez-Sargent et al. the increased incidence of cataract in Dahl-salt sensitive rats(DSR) was due to increasd water and sodium contents and decreased potassium content. In this investigative study on hypertension, the water, Sodium and potassium contents in Spontaneous Hypertensive Rats(SHR) were measured. After treatment with nifedipine in SHR, we observed decreased blood pressure along with the changes in water, sodium and potassium contents of the lenses. The following results were obtained from our experiments. 1. In normal SDR, The blood pressure did not decrease with nifedipine injection. 2. After 3-7 days of nifedipine injection bidaily, the blood pressure of SHR did not decrease. 3. After 2 weeks of nifedipine injection bidaily, the blood pressure of the SHR decreased slightly and after 4 weeks of nifedipine injection bidaily, the blood pressure of SHR decreased significantly. 4. Water and sodium contents of SHR were higher than that of SDR and the potassium content was similar to that of SDR. 5. The elevated water and sodium contents of SHR decreased along with decrease of blood pressure, and after 2 weeks of nifedipine injection, showed similar level as the contents of SDR lenses. 6. Potassium contents of SHR lenses showed no change were similar to SDR lines except the 4 weeks nifedipine injection group which showed higher potasslum contents.

Establishment of the DOCA-Salt hypertensive rat model / 中国药理学通报

Aim To establish a reliable and practical rat model with hypertension induced by DOCA-Salt.Methods One week after nephrectomy,the rats were subcutaneously injected with DOCA (30 mg?kg-1) once a week and fed with a chaw with 10 g?L-1NaCl plus 2 g?L-1 KCl in drinking water for 4 weeks. Blood pressure was measured and,urine was collected for measurement of volume(UV),UNaV,UClV,UKV,UCaV and pH values,once a week. SGPT,CREA,SUGA,TRIG,CHOL,INS,ALD,ADH were measured in circulating blood samples. Kidney morphological changes and Na+,K+-ATPase activity of the renal tubular epithelial cells were also examined. Results Blood pressure,UV,UNaV and UClV were increased and histopathological changes of the kidney such as glomerulus sclerosis and tubular pachynsis were observed in the DOCA-Salt rats. Whereas UKV,UCaV,urine pH values,SGPT,CREA,SUGA,TRIG,CHOL,INS,ALD and ADH were not changed. In contrast,Na+,K+-ATPase activity of the renal tubular epithelial cells was decreased. Conclusion DOCA-Salt is a reliable hypertensive model with sodium retention.