A5004935510- Sodium Intake and Health
- Hormonal Regulation and Hypertension
- Blood Pressure and Hypertension Studies
- Renin-Angiotensin System Studies
- Heart Rate Variability and Autonomic Control
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Stress Responses and Cortisol
- Neuroinflammation and Neurodegeneration Mechanisms
- Adipokines, Inflammation, and Metabolic Diseases
- Atherosclerosis and Cardiovascular Diseases
- Cardiovascular Disease and Adiposity
- Congenital heart defects research
- Birth, Development, and Health
- Immune Cell Function and Interaction
- Thermoregulation and physiological responses
- Renal and related cancers
- Apelin-related biomedical research
- Eicosanoids and Hypertension Pharmacology
- Immune cells in cancer
- Health and Lifestyle Studies
- Adipose Tissue and Metabolism
- Hydrogen's biological and therapeutic effects
- Nutritional Studies and Diet
- Neuroscience of respiration and sleep
- Circadian rhythm and melatonin
Vanderbilt University Medical Center
2016-2020
ARCA Biopharma (United States)
2020
University of Minnesota
2011-2018
Vanderbilt University
2015-2018
University of Minnesota Medical Center
2017
Mansoura University
2015-2016
Universidade Estadual de Campinas (UNICAMP)
2016
Cedars-Sinai Medical Center
2016
Tulane University
2016
Saint Louis University
2016
Sodium accumulates in the interstitium and promotes inflammation through poorly defined mechanisms. We describe a pathway by which sodium enters dendritic cells (DCs) amiloride-sensitive channels including alpha gamma subunits of epithelial channel hydrogen exchanger 1. This leads to calcium influx via exchanger, activation protein kinase C (PKC), phosphorylation p47phox, association p47phox with gp91phox. The assembled NADPH oxidase produces superoxide subsequent formation immunogenic...
Inflammation and adaptive immunity play a crucial role in the development of hypertension. Angiotensin II probably other hypertensive stimuli activate central nervous system promote T-cell activation end-organ damage peripheral tissues.To determine if renal sympathetic nerves mediate inflammation hypertension.Bilateral denervation using phenol application to arteries reduced norepinephrine levels blunted angiotensin II-induced Bilateral also inflammation, as reflected by decreased...
Rationale: Accumulating evidence supports a role of adaptive immunity and particularly T cells in the pathogenesis hypertension. Formation memory cells, which requires costimulatory molecule CD70 on antigen-presenting is cardinal feature immunity. Objective: To test hypothesis that immunologic contribute to blood pressure elevation renal dysfunction mediated by repeated hypertensive challenges. Methods Results: We imposed challenges using either N ω -nitro-L-arginine methyl ester...
Renal sympathetic denervation (RDNx) has emerged as a novel therapy for hypertension; however, the therapeutic mechanisms remain unclear. Efferent renal nerve activity recently been implicated in trafficking inflammatory immune cells and chemokine cytokine release. Several of these mediators are known to activate or sensitize afferent nerves. This study aimed elucidate roles efferent nerves inflammation hypertension deoxycorticosterone acetate (DOCA) salt rat model. Uninephrectomized male...
Renal denervation has been shown to lower arterial pressure in some hypertensive patients, yet it remains unclear whether this is due ablation of afferent or efferent renal nerves. To investigate the role nerves regulation, previous studies have used methods that disrupt both and nonrenal signaling. The present study was conducted develop validate a technique for selective does not other pathways. do this, we adapted sensory adrenal gland by topical application capsaicin tested hypothesis...
The sympathetic nervous system plays an important role in some forms of human hypertension as well the Dahl salt-sensitive rat model hypertension; however, targets involved remain unclear. To address this, we examined renal and splanchnic nerves by performing sham surgery (n=10) or targeted ablation (renal denervation, n=11), (celiac ganglionectomy, both (n=11) hypertensive rats. Mean arterial pressure increased from ≈120 mm Hg, while on a 0.1% sodium chloride diet, to ≈140 Hg after being...
Prior studies have focused on the role of kidney and vasculature in salt-induced modulation blood pressure; however, recent data indicate that sodium accumulates tissues can activate immune cells. We sought to examine mechanisms by which salt causes activation human monocytes both vivo vitro.To study effect monocytes, were isolated from volunteers perform several vitro experiments. Exposure elevated Na+ex caused a co-ordinated response involving isolevuglandin (IsoLG)-adduct formation,...
Clinical data suggest that renal denervation (RDNX) may be an effective treatment for human hypertension; however, it is unclear whether this therapeutic effect due to ablation of afferent or efferent nerves. We have previously shown RDNX lowers arterial pressure in hypertensive Dahl salt-sensitive (S) rats a similar degree observed clinical trials. In addition, we recently developed method selective nerves (renal-CAP). the present study, tested hypothesis antihypertensive S rat by comparing...
Effector memory T lymphocytes (T
T and B cells have been implicated in hypertension, but the mechanisms by which they produce a coordinated response is unknown. follicular helper (Tfh) that interleukin 21 (IL21) promote germinal center (GC) cell responses leading to immunoglobulin (Ig) production. Here we investigate role of IL21 Tfh hypertension. In angiotensin (Ang) II-induced production increased, Il21-/- mice develop blunted attenuated vascular end-organ damage, decreased 17A (IL17A) interferon gamma Tfh-like GC...
Hypertension often occurs in concurrence with obesity and diabetes mellitus, commonly referred to as metabolic syndrome. Renal denervation (RDNx) lowers arterial pressure (AP) improves glucose metabolism drug-resistant hypertensive patients high body mass index. In addition, RDNx has been shown reduce renal inflammation the mouse model of angiotensin II hypertension. The present study tested hypothesis that reduces AP obesity-induced Eight-week-old C57BL/6J mice were fed either a low-fat...
Hypertension is the leading modifiable risk factor for death worldwide, yet causes remain unclear and treatment remains suboptimal. Catheter-based renal denervation (RDNX) a promising new resistant hypertension, but mechanisms underlying its antihypertensive effect unclear. We recently found that RDNX attenuates deoxycorticosterone acetate-salt hypertension this dependent on ablation of afferent nerves associated with decreased inflammation. To determine if common to other models...
Juxtaglomerular (JG) cells, major sources of renin, differentiate from metanephric mesenchymal cells that give rise to JG or a subset smooth muscle the renal afferent arteriole. During periods dehydration and salt deprivation, stromal (MSCs) cells. undergo expansion redifferentiate express renin along Gene expression profiling comparing resident MSCs with indicates transcription factor Sox6 is highly expressed in adult kidney. In vitro, loss reduces differentiation renin-producing vivo,...
High blood pressure is a major modifiable risk factor for cardiovascular disease (CVD) which the leading cause of death worldwide. Excessive salt intake and inflammation are implicated in genesis hypertension. It has recently become evident that sodium accumulates interstitial space can promote through poorly defined mechanisms. We published new pathway increased oxidative stress dendritic cells (DCs) leads to formation isoketal‐modified proteins act as neo‐antigens activate T cells....
Sodium can accumulate in the interstitium and promote inflammation through poorly defined mechanisms. Here we describe a novel pathway by which dendritic cells (DCs) are activated increased extracellular sodium (190 mM). We show that entry epithelial channel (ENaC) hydrogen exchanger (NHE) leads to calcium influx via exchanger, activation of protein kinase C (PKC), phosphorylation p47phox association with gp91phox. The assembled NADPH oxidase produces superoxide subsequent formation...
Both inflammation and dietary salt intake have been implicated in the pathogenesis of hypertension. We previously shown that formation immunogenic isoketal‐protein adducts dendritic cells (DCs) plays an important role development experimental Recently, it has can accumulate interstitial space promote inflammation. In current study, we tested hypothesis exposure to high drives DCs toward activated state, leading production isoketals promotion To test this hypothesis, mouse splenic were...
Renal nerves contribute to some forms of hypertension, but the differential role afferent and efferent renal remains unclear. It has been proposed that modulate arterial pressure (AP) since rats subjected dorsal rhizotomy (DRX) at spinal levels T9-L1 exhibit salt-sensitive hypertension. Since DRX is not selective for afferents, we developed a novel method ablation calcitonin gene-related peptide (CGRP) positive sensory fibers in kidney tested hypothesis that, as with DRX, our denervation...
Hypertension (HTN) is a global epidemic and often occurs in concurrence with obesity diabetes (i.e. metabolic syndrome). Recent clinical trials suggest that renal denervation (RDNX) decreases blood pressure (BP) improves glucose metabolism drug resistant hypertensive patients. Using murine model we tested the hypothesis associated inflammation secondary to T cell infiltration, which activates sensory nerves increases sympathetic activity. 8‐week old C57Bl6 mice were fed either low fat diet...
Renal denervation (RDNX) attenuates hypertension (HT) in some animal models and human patients, yet the antihypertensive mechanisms involved are not known. Because it has been suggested that efferent renal nerves may cause recruitment of T lymphocytes (T cells) into kidneys, cell-secreted cytokines can activate afferent neurons, we hypothesized RDNX HT angiotensin II (AngII)-salt deoxycorticosterone acetate (DOCA)-salt by decreasing nerve-dependent cell trafficking to kidneys cell-mediated...
Renal denervation (RDNX) attenuates drug resistant hypertension (HT) in humans, but it is unclear whether this due to ablation of afferent or efferent renal nerves. We have previously shown that RDNX the intravenous (IV) AngII‐salt model HT rat. The present study tested hypothesis antihypertensive effect IV nerves, specifically. Male Sprague Dawley rats underwent SHAM surgery, selective nerves by periaxonal capsaicin (renal‐CAP). Rats were instrumented with an catheter for delivery AngII and...
Similar to humans, renal denervation (RDNX) attenuates hypertension (HT) in the Dahl salt‐sensitive (DS) rat, yet it is unclear whether this effect due ablation of afferent or efferent nerves (or both). The present study tested hypothesis that antihypertensive RDNX early phase (3 weeks high salt diet) DS HT nerves, specifically. rats on a low diet (0.1% NaCl) were instrumented for telemetric measurement arterial pressure (AP) and heart rate (HR), housed metabolic cages Na+ H2O balance....