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PubMed2004

Patients with systemic lupus erythematosus have abnormally elevated Epstein-Barr virus load in blood.

Various genetic and environmental factors appear to be involved in systemic lupus erythematosus (SLE). Epstein-Barr virus (EBV) is among the environmental factors that are suspected of predisposing to SLE, based on the characteristics of EBV itself and on sequence homologies between autoantigens and EBV antigens. In addition, higher titers of anti-EBV antibodies and increased EBV seroconversion rates have been observed in SLE patients as compared with healthy control individuals. Serologic responses do not directly reflect EBV status within the body. Clarification of the precise status of EBV infection in SLE patients would help to improve our understanding of the role played by EBV in this disease. In the present study we determined EBV types in SLE patients (n = 66) and normal control individual (n = 63) by direct PCR analysis of mouthwash samples. We also compared EBV load in blood between SLE patients (n = 24) and healthy control individuals (n = 29) using semiquantitative PCR assay. The number of infections and EBV type distribution were similar between adult SLE patients and healthy control individuals (98.5% versus 94%). Interestingly, the EBV burden in peripheral blood mononuclear cells (PBMCs) was over 15-fold greater in SLE patients than in healthy control individuals (mean +/- standard deviation: 463 +/- 570 EBV genome copies/3 microg PBMC DNA versus 30 +/- 29 EBV genome copies/3 microg PBMC DNA; P = 0.001), suggesting that EBV infection is abnormally regulated in SLE. The abnormally increased proportion of EBV-infected B cells in the SLE patients may contribute to enhanced autoantibody production in this disease.

Burkitt Lymphoma↗
PubMed1999

Cortical tibial bone volume in two strains of mice: effects of sciatic neurectomy and genetic regulation of bone response to mechanical loading.

Although C3H/HeJ (C3H) and C57BL/6J (B6) mice are similar in body size (and adult weight), and have bones of similar external size, C3H mice have higher peak bone densities than B6 mice (e.g., 53% higher peak bone density in the femora). The current studies were intended to assess the role of mechanical loading/unloading as a possible determinant of the bone density difference between these inbred strains of mice and, specifically, to assess the effect of sciatic neurectomy on histomorphometric indices of bone formation and resorption in the tibiae of female C3H and B6 mice. Groups of 10 mice of each strain were subjected to left-side sciatic neurectomy (left hindlimb immobilization) or a sham procedure. The contralateral (right) legs of each mouse were used as controls. Four weeks of immobilization produced no systemic changes in bone formation indices in either strain of mice (i.e., no change in serum alkaline phosphatase or serum osteocalcin). However, histomorphometric assessments at the tibiofibular junction showed that 4 weeks of immobilization caused a time-dependent decrease in the length of the endosteal bone forming perimeter (e.g., 14% of control single-labeled, noneroded surface at 4 weeks, p < 0.005) with a concomitant increase in the length of the endosteal bone resorbing perimeter (i.e., 424% of control eroded surface at 4 weeks, p < 0.005), in the B6 mice. These effects were associated with an increase in medullary area (132% of control, p < 0.05) at this site, in the B6 mice. The pattern of response was different in the tibiae of the C3 mice-a much smaller decrease in bone forming perimeter (88% of control at 4 weeks, p < 0.05), with no associated increase in bone resorbing perimeter, and no change in medullary area. Similar effects were seen at a second cross-sectional sampling site, in the proximal tibia. Together, these findings indicate that B6 mice are more sensitive to endosteal bone loss from hindlimb immobilization than C3H mice.

Alkaline Phosphatase↗
PubMed1990

Pantothenic acid, acute ethanol consumption and sulphadimidine acetylation.

The effect of pantothenic acid and acute ethanol loading on the genetically determined N-acetyltransferase activity has been studied using sulphadimidine as a test substance. The administration of 1100 mg pantothenic acid daily (600 mg orally, 500 mg iv) for seven days did not significantly alter sulphadimidine kinetics in the primarily elderly 21 subjects we investigated. Acute ethanol loading (0.73 g/kg pure alcohol at start and 0.11 g/kg pure alcohol hourly for 8 hours afterwards, stock solution: 20% v/v ethanol in fruit juice) did not change sulphadimidine acetylation in 10 healthy male volunteers. It is concluded that despite theoretical assumptions exogenous factors like pantothenic acid and ethanol do not significantly influence the cytosolic N-acetyltransferase activity. Consequently they do not interfere with the acetylator phenotyping procedure.

Acetylation↗
PubMed1998

Prevention of salt-dependent cardiac remodeling and enhanced gene expression in stroke-prone hypertensive rats by the long-acting calcium channel blocker lacidipine.

OBJECTIVE: To analyze the effect of the long-acting calcium channel blocker lacidipine on cardiovascular remodeling induced by salt loading in a genetic model of hypertension. DESIGN: We examined the influence of threshold doses of lacidipine, with little blood-pressure lowering effect, on cardiac weight and gene expression in stroke-prone spontaneously hypertensive rats (SHRSP). METHODS: SHRSPs (8-week-old) were randomly allocated to four groups: control, salt-loaded SHRSP and salt-loaded SHRSP treated with lacidipine at 0.3 and 1 mg/kg per day. Systolic blood pressure was measured by the tail-cuff method. At the end of 6 weeks of treatment, ventricles were collected and weighed. Ventricular messenger RNA was extracted and subjected to Northern blot analysis. RESULTS: Lacidipine (0.3 mg/kg per day) not only prevented the salt-dependent cardiac hypertrophy and the slight increase in systolic blood pressure induced by salt, but also prevented, largely or completely, salt-dependent increases in ventricular levels of several gene products: skeletal and cardiac alpha-actin, beta-myosin heavy chain (beta-MHC), type I collagen, long-lasting (L)-type calcium channel and preproendothelin-1. At a higher dose of 1 mg/kg per day, lacidipine further decreased systolic blood pressure below the level of control SHRSP, completely prevented salt-dependent overexpression of the beta-MHC gene and markedly attenuated salt-dependent overexpression of the transforming growth factor-beta1 gene. CONCLUSIONS: Lacidipine prevents the cardiac remodeling and enhanced gene expression induced by salt loading in SHRSP at doses that only minimally affect the high systolic blood pressure.

Animals↗
PubMed2003

The genetic background as a determinant of human T-cell leukemia virus type 1 proviral load.

Human T-cell leukemia virus type 1 (HTLV-1) is etiologically linked with HTLV-1-associated diseases. HTLV-1 proviral load is higher in persons with adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis than in asymptomatic carriers. However there are little data available on the factors controlling HTLV-1 proviral load in carriers. To study the effect of genetic background on HTLV-1 proviral load, we employed a mouse model of HTLV-1 infection that we had established. Here we analyzed nine strains of mice and found there is a great variation of proviral load among mouse strains that is not necessarily dependent on major histocompatibility complex. The antibody response is also different among these strains. To our knowledge, this is the first demonstration of the importance of the genetic background other than major histocompatibility complex controlling the HTLV-1 proviral load.

Animals↗
PubMed2000

The alpha2-macroglobulin gene in AD: a population-based study and meta-analysis.

BACKGROUND: Whereas several authors recently reported a positive association between the alpha2-macroglobulin gene (A2M) and late-onset AD (LOAD), others were unable to replicate these findings. Early-onset AD (EOAD) is defined as onset age <65 years. Virtually all patients with LOAD are >65 years of age. OBJECTIVE: To evaluate the role of A2M in AD, the authors conducted a population-based study of EOAD and LOAD as well as a meta-analysis of all studies conducted to date. METHODS: Patients with EOAD (n = 100) were derived from a population-based study in four northern provinces of the Netherlands and the area of metropolitan Rotterdam. Patients with LOAD (n = 344) were drawn from the Rotterdam Study, a population-based prospective study on residents aged 55 years and over of a Rotterdam suburb in the Netherlands. Two polymorphisms were studied, A2M-I/D and A2M-Ile1000Val, in relation to the APOE epsilon4 allele (APOE*4). RESULTS: No genotypic or allelic association was found for either polymorphism in the population-based series of patients with LOAD. In patients with EOAD without APOE*4, a significant increase of carriers of A2M-1000Val was found. The meta-analysis of available published case-control data on these polymorphisms in white and mixed ethnic populations yielded no significant differences between cases and controls. Pooling the Asian studies conducted to date showed a significant decrease in the frequency of A2M-D among patients. CONCLUSIONS: These results suggest that A2M is not genetically associated with LOAD in white patients or mixed populations as found in the United States. In these populations A2M does not have clinical relevance. From a scientific perspective, the findings on EOAD and Asian patients require replication and further research in the A2M region.

Aged↗
PubMed1996

Vascular smooth muscle polyploidy and cardiac hypertrophy in genetic hypertension.

We studied the mechanisms responsible for vascular and cardiac hypertrophy in hypertension (pressure load and humoral and genetic factors) in two experimental approaches: (1) We carried out a cosegregation analysis to correlate cardiac and vascular hypertrophy with subphenotypes of blood pressure in an F2 generation of a cross between stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats; (2) we treated 8-week-old SHRSP with perindopril, an angiotensin-converting enzyme inhibitor; losartan, an angiotensin type 1 receptor antagonist; or perindopril combined with a nitric oxide synthase inhibitor to investigate the relative contributions of blood pressure and angiotensin II to the pathogenesis of cardiac hypertrophy and vascular smooth muscle polyploidy. Vascular smooth muscle polyploidy was measured with flow cytometry DNA analysis. Cardiac hypertrophy was assessed by measuring the ratios of heart weight to body weight and left ventricle + septum weight to body weight. Blood pressure was measured with radiotelemetry in the F2 cosegregation experiment and with tail-cuff plethysmography in the pharmacological study. In the F2 rats, the best predictor of smooth muscle polyploidy by ANCOVA was systolic pressure (F=29.28, P < .0001). The ratio of left ventricle + septum weight to body weight had four major predictors: the male progenitor of the cross, sex, pulse pressure, and change in systolic pressure during salt (F=43.67, P < .0001; F=16.37, P < .0001; F=8.41, P=.0022; and F=12.39, P= .0003, respectively). The ratio of heart weight to body weight had similar predictors. In the pharmacological study, treatment with losartan alone, perindopril alone, or perindopril in combination with N(G)-nitro-L-arginine methyl ester prevented the development of smooth muscle polyploidy and cardiac hypertrophy. The prevention of cardiac hypertrophy was most marked in the SHRSP treated with perindopril plus N(G)-nitro-L-arginine methyl ester, despite blood pressure being higher in this group than in the two other treatment groups. We conclude that vascular and cardiac hypertrophy in this form of hypertension are regulated by different variables. However, suppression of the action of angiotensin II lessens hypertrophy of both types of muscle.

Angiotensin II↗
PubMed2006

Belgrade rats display liver iron loading.

Patients with mutations in divalent metal transporter-1 (DMT1), an intestinal nonheme iron transporter, suffer from microcytic anemia and hepatic iron loading. DMT1 is also mutated in Belgrade rats, an animal model with a thalassemic-like disorder of microcytic anemia with hyperferrinemia. However, aspects of hepatic iron loading in this genetic model are not well characterized. To more fully define the Belgrade rat's iron status, we compared the characteristics of homozygous (b/b) and heterozygous (b/+) rats fed an iron-supplemented diet for 3 wk postweaning. Dietary supplementation with ferrous iron improved the anemia of b/b rats insofar as hematocrits increased from 0.13 (21-d-old) to 0.31 (42-d-old). However, hematocrits remained significantly lower than those of age-matched b/+ rats (0.36 and 0.41 in 21- and 42-d-old heterozygotes, respectively, P < 0.05). Wright's staining of b/b red cells confirmed the hypochromic microcytic nature of Belgrade rats' anemia. The liver iron concentration of 42-d-old b/b rats was greater than in age-matched b/+ rats (5.97 vs. 2.24 mumol/g, P < 0.05). Whereas Perls' Prussian blue iron staining was evident in both periportal and centrilobular regions in 42-d-old b/b liver sections, no staining was observed in age-matched b/+ tissue sections. Quantitative real-time PCR analysis showed that expression of liver hepcidin mRNA in 42-d-old b/b rats was 3-fold greater than age-matched b/+ rats. These results indicate that, similar to human patients with DMT1 mutations, Belgrade rats also display hepatic iron loading. Our data suggest this condition arises from ineffective erythropoiesis.

Animals↗
PubMed2006

Hereditary iron overload: update on pathophysiology, diagnosis, and treatment.

Hereditary hemochromatosis, a very common genetic defect in the Caucasian population, is characterized by progressive tissue iron overload which leads to irreversible organ damage if it is not treated timely. The elucidation of the molecular pathways of iron transport through cells and its control has led to the understanding of various genetic iron-loading conditions. Four types of inherited iron overload have been recognized: type 1, the most common form with an autosomal recessive inheritance, is associated with mutations in the HFE gene on chromosome 6; type 2 (juvenile hemochromatosis) is an autosomal recessive disorder with causative mutations identified in the HJV gene (subtype A) on chromosome 1 and the HAMP gene (subtype B) on chromosome 19; type 3 has also an autosomal recessive inheritance with mutations in the TfR2 gene on chromosome 3; type 4 is an autosomal dominant condition with heterozygous mutations in the ferroportin 1 gene on chromosome 2. In this review, the genetics, pathophysiology, diagnosis, clinical features, and management of these different types of hereditary hemochromatosis are briefly discussed.

Antimicrobial Cationic Peptides↗
PubMed2026

Genomic dimensions deconstruct the clinical heterogeneity of bipolar disorder.

Bipolar disorder's (BD) clinical heterogeneity has an unresolved genetic basis. We meta-analyzed genome-wide association studies (GWAS) of 16 BD subphenotypes in 226,032 individuals from 57 cohorts (38,022 cases); 10 advanced to multivariate and multi-trait analyses. Four factors (compulsive, psychotic, dysregulated, internalizing) explained 82.8% of shared genetic variance. BD1 and BD2 loaded on distinct factors despite a high genetic correlation; 87.0% of common-factor loci were significant in neither subtype. Unipolar mania aligned with psychosis over internalizing, and was distinguishable from BD1, and rapid cycling showed heritable cross-domain liability. We identified 356 risk loci, 158 novel, including the first univariate-GWAS associations for psychosis, unipolar mania, rapid cycling and schizoaffective disorder-and 249 credible genes (89 high-confidence), 12 with approved-drug or clinical-phase annotations. Cell-type association showed a midbrain dopaminergic-GABAergic gradient along the psychotic factor. BD's genetic architecture appears hierarchical-a general liability resolving into dimensions of course and comorbidity, beyond subtypes.

Journal Article↗
PubMed2002

Genetic haemochromatosis: genes and mutations associated with iron loading.

Haemochromatosis is an autosomal recessive disorder common among Caucasians that leads to iron overload. Molecular studies have shown that the disease is prevalently due to a mutation in the HFE gene. Although C282Y in the homozygous state remains the most common patient's genotype, other genes and genetic mutations are associated with haemochromatosis. Haemochromatosis type 2, a severe form with juvenile onset, is due to mutations in an unidentified gene on chromosome 1q. Haemochromatosis type 3 is linked to a locus on 7q22 and is due to mutations in the transferrin receptor 2. Haemochromatosis type 4, the only autosomal dominant form, is caused by mutations in ferroportin 1 on 2q32. The genes responsible for African and neonatal forms of iron overload are still unknown. The identification of all of the genes associated with haemochromatosis is critical for molecular-based diagnosis and central to our understanding of the regulation of iron homeostasis.

Cation Transport Proteins↗
PubMed1993

Tissue iron loading and histopathological changes in hypotransferrinaemic mice.

Tissue iron loading in hypotransferrinaemic (hpx/hpx) mice was investigated as a model for genetic (primary) haemochromatosis. Iron loading of liver preceded that in the pancreas and heart. One-year-old hpx/hpx mice showed iron staining in exocrine pancreas, liver parenchymal cells, and cardiac and intestinal smooth muscle cells. Iron-loaded macrophages were observed in all these tissues. Islets of Langerhans, biliary epithelial cells, and spleen were iron-free. The pancreas was fibrotic with massive macrophage infiltration and loss of secretory epithelium. Liver showed evidence of chronic inflammatory infiltration with increased collagen fibres in the parenchymal region but no cirrhosis. Serum aspartate aminotransferase activity and plasma glucose were increased in hpx/hpx compared with wild-type mice. Heavy iron loading with haemosiderin deposition in the liver could be demonstrated in hpx/hpx mice from 6 weeks of age. Heterozygous hypotransferrinaemic mice showed minor increases in liver iron stores at 6-12 weeks, but not at 1 year of age. Serum ferritin levels in heterozygous mice were also increased at 6-8 weeks of age. It was concluded that 1-year-old hpx/hpx mice showed evidence of liver and pancreatic damage secondary to tissue iron overload. The iron loading pattern and tissue damage showed some features which were distinct from those observed in haemochromatosis.

Animals↗
PubMed2003

The structure of genetic and environmental risk factors for common psychiatric and substance use disorders in men and women.

BACKGROUND: Patterns of comorbidity suggest that the common psychiatric and substance use syndromes may be divisible into 2 broad groups of internalizing and externalizing disorders. We do not know how genetic and environmental risk factors contribute to this pattern of comorbidity or whether the etiologic structure of these groups differ in men and women. METHODS: Lifetime diagnoses for 10 psychiatric syndromes were obtained at a personal interview in more than 5600 members of male-male and female-female twin pairs ascertained from a population-based registry. Multivariate twin modeling was performed using the program Mx. RESULTS: We first fit models to the following 7 syndromes: major depression, generalized anxiety disorder, phobia, alcohol dependence, drug abuse/dependence, adult antisocial behavior, and conduct disorder. The full model, which could be constrained to equality in male and female subjects, identified 2 genetic factors. The first had strongest loadings on alcohol dependence, drug abuse/dependence, adult antisocial behavior, and conduct disorder; the second, on major depression, generalized anxiety disorder, and phobia. Alcohol dependence and drug abuse/dependence had substantial disorder-specific genetic risk factors. Shared environmental factors were most pronounced for conduct disorder and adult antisocial behavior. No clear internalizing/externalizing structure was seen for the unique environmental common factors. We then fit models to 5 internalizing syndromes. The full model, which could also be constrained to equality in men and women, revealed one genetic factor loading most heavily on major depression and generalized anxiety disorder and another loading most strongly on animal and situational phobia. CONCLUSIONS: The underlying structure of the genetic and environmental risk factors for the common psychiatric and drug abuse disorders in men and women is very similar. Genetic risk factors predispose to 2 broad groups of internalizing and externalizing disorders. Within the internalizing disorders, 2 genetic factors are seen that predispose to disorders dominated by anxious-misery and fear. Substance use disorders have disorder-specific genetic risks. The externalizing disorders of conduct disorder and adult antisocial behavior are significantly influenced by the shared environment. The pattern of lifetime comorbidity of common psychiatric and substance use disorders results largely from the effects of genetic risk factors.

Adult↗
PubMed2001

Lentivirus-transduced human monocyte-derived dendritic cells efficiently stimulate antigen-specific cytotoxic T lymphocytes.

Dendritic cells (DCs) are professional antigen-presenting cells that are highly effective adjuvants for immunizing against pathogens and tumor antigens. The potential merit of genetic approaches to loading DCs with antigens is to express high and sustained levels of proteins that can be subsequently processed and presented to T lymphocytes. Replication-defective oncoretroviruses are able to efficiently transduce CD34(+) progenitor-derived DCs but not monocyte-derived DCs. Here, it is shown that efficient gene transfer is obtained using a human immunodeficiency virus-1-derived lentiviral vector deleted of all structural and accessory genes. Infection of immature DCs with the lentiviral vector at a multiplicity of infection of 20 resulted in stable gene expression in 30% to 40% of the matured DCs. Proviral DNA was detectable by Alu polymerase chain reaction for the lentiviral but not the oncoretroviral vector. Most importantly, it is demonstrated that lentivirus-transduced DCs were fully functional and effectively activated autologous HLA A2.1(+) peripheral blood cytotoxic T lymphocytes (CTLs). DCs expressing lentiviral vector-encoded Flu peptide were at least as efficient as DCs pulsed with the same peptide in stimulating specific CTLs. The efficacy of the lentivirus-transduced DCs was further demonstrated by their ability to directly activate freshly harvested peripheral blood Flu-specific CTLs in the absence of CD4(+) T-cell help and exogenous cytokines. The availability of a stable gene delivery system based on a multiply attenuated lentivirus that does not encode any viral protein and that allows sustained antigen presentation by DCs derived from blood monocytes will be very useful for the biologic investigation of DCs and the improvement of immunotherapeutic strategies involving DCs.

CD4-Positive T-Lymphocytes↗
PubMed2025

The downregulation of ubiquitin-specific peptidase 2 indicates a poor prognosis and promotes the progression of gastric cancer through focal adhesion and ECM pathway signaling.

Gastric cancer ranks among the most prevalent forms of cancer worldwide. Recent rapid advancements in diagnostic methods, neoadjuvant or adjuvant therapies, and surgical procedures have significantly improved survival rates for patients with gastric cancer. Nonetheless, these benefits have not yet reached the majority of individuals affected. Previous research has indicated that USP2, a component of the ubiquitin system, plays a crucial role in reshaping the proteome and enhancing the prognosis of diseases. However, the current understanding of USP2 expression and the associated pathways in gastric cancer remains unclear. The differential expression of USP2 was examined in pan-cancer, with a particular focus on its expression in gastric cancer cells and patients. Additionally, the impact of USP2 on the proliferation, migration, and apoptosis of gastric cancer cells was explored via CCK8, transwell, and invasion assays. RNA sequencing was employed to investigate pathways associated with USP2, and RT-qPCR and western blotting were utilized to confirm the expression of related pathway genes and proteins. The prognostic value of a model derived from USP2 expression was assessed and validated. USP2 expression was significantly reduced in gastric cancer cells and patient samples (p&#x2009;<&#x2009;0.05). Patients with low USP2 expression are primarily associated with genetic variations, neoantigen loads, microsatellite instability (MSI) scores, and immune cell infiltration (p&#x2009;<&#x2009;0.05). The overexpression of USP2 suppresses proliferation, migration, and cell cycle progression while enhancing apoptosis in GC cells. Concurrently, we identified 865 genes whose expression was downregulated. KEGG and GSEA enrichment analyses revealed significant suppression of the focal adhesion and ECM receptor interaction pathways following USP2 overexpression. A genomic model derived from USP2 was constructed and validated for its reliability in predicting patient prognosis. The expression of USP2 was positively correlated with sensitivity to small-molecule drugs, including entinostat, SB590885, and PF-562,271. USP2 acts as a negative regulator of gastric cancer progression. Consequently, USP2 has the potential to be utilized as a therapeutic target to improve the clinical prognosis and survival rates of patients.

Humans↗
PubMed1979

Bilirubin diglucuronide synthesis by a UDP-glucuronic acid-dependent enzyme system in rat liver microsomes.

Incubation of rat liver homogenate or microsomal preparations with bilirubin or bilirubin monoglucuronide with (BMG) resulted in formation of bilirubin diglucuronide (BDG). Both synthesis of BMG and its conversion to BDG were critically dependent on the presence of UDP-glucuronic acid. Pretreatment of the animals with phenobarbital stimulated both reactions. When 33 microM bilirubin was incubated with microsomal preparations from phenobarbital-treated rats, 80-90% of the substrate was converted to bilirubin glucuronides; the reaction products consisted of almost equal amounts of BMG and BDG. When phenobarbital pretreatment was omitted or when the substrate concentration was increased to 164 microM bilirubin, proportionally more BMG and less BDG were formed. Homogenate and microsomes from homozygous Gunn rats neither synthesized BMG nor converted BMG to BDG. These findings in vitro suggest an explanation for the observations in vivo that, in conditions of excess bilirubin load or of genetically decreased bilirubin UDP glucuronosyltransferase (EC 2.4.1.17) activity, proportionally more BMG and less BDG are excreted in bile.

Animals↗
PubMed2003

Altered renal handling of sodium in human hypertension: short review of the evidence.

A pathogenic role of the kidney in hypertension has been strongly supported by experimental studies by Guyton and Dahl since the 1960s. In the early 1980s, de Wardener and MacGregor proposed that in hypertensive patients the ability of the kidneys to excrete a sodium load could be genetically impaired. Since then, "sodium-sensitive" hypertension has been the object of numerous studies, mostly on animal models because of the difficulty to investigate the renal handling of sodium in humans. More recently, considerable progress in this field has been made thanks to the in vivo study of segmental renal tubular function by the clearance of lithium and to the growing knowledge of the genetics of renal tubular sodium transport systems. The scope of this review is to briefly review the most relevant information gathered by the investigation of segmental renal tubular sodium handling in humans as related to blood pressure regulation and hypertension. In aggregate, the results of these studies strongly support the association between altered renal sodium handling and high blood pressure and suggest a causal role of genetic, nutritional, metabolic, and neurohormonal factors. All of these factors, alone or in combination, may be able to impair the normal renal tubular sodium handling and influence blood pressure homeostasis. The paradigm of the pathogenic role of the kidney in hypertension is thus relentlessly shifting toward the definition of inherited as well as acquired renal tubular defects and molecular alterations, providing a plausible explanation for the alteration in blood pressure levels.

Blood Pressure↗