Medicine and Health Sciences Commons^™

Involvement Of Reactive Oxygen Species In A Feed-Forward Mechanism Of Na/K-Atpase Mediated Signaling, Yanling Yan, Anna P. Shapiro, Steven Haller, Vinal Katragadda, Lijun Liu, Jiang Tian, Venkatesha Basrur, Deepak Malhotra, Zi-Jian Xie, Nader G. Abraham, Joseph I. Shapiro Md, Jiang Liu

Yanling Yan

Cardiotonic steroids (such as ouabain) signaling through Na/K-ATPase regulate sodium reabsorption in the renal proximal tubule. We report here that reactive oxygen species are required to initiate ouabain-stimulated Na/K-ATPase·c-Src signaling. Pretreatment with the antioxidant N-acetyl-L-cysteine prevented ouabain-stimulated Na/K-ATPase·c-Src signaling, protein carbonylation, redistribution of Na/K-ATPase and sodium/proton exchanger isoform 3, and inhibition of active transepithelial ²²Na⁺ transport. Disruption of the Na/K-ATPase·c-Src signaling complex attenuated ouabain-stimulated protein carbonylation. Ouabain-stimulated protein carbonylation is reversed after removal of ouabain, and this reversibility is largely independent of de novo protein synthesis and degradation by either the lysosome or the proteasome pathways. Furthermore, …

Involvement Of Reactive Oxygen Species In A Feed-Forward Mechanism Of Na/K-Atpase Mediated Signaling, Yanling Yan, Anna P. Shapiro, Steven Haller, Vinal Katragadda, Lijun Liu, Jiang Tian, Venkatesha Basrur, Deepak Malhotra, Zi-Jian Xie, Nader G. Abraham, Joseph I. Shapiro Md, Jiang Liu

Zijian Xie

Cardiotonic steroids (such as ouabain) signaling through Na/K-ATPase regulate sodium reabsorption in the renal proximal tubule. We report here that reactive oxygen species are required to initiate ouabain-stimulated Na/K-ATPase·c-Src signaling. Pretreatment with the antioxidant N-acetyl-L-cysteine prevented ouabain-stimulated Na/K-ATPase·c-Src signaling, protein carbonylation, redistribution of Na/K-ATPase and sodium/proton exchanger isoform 3, and inhibition of active transepithelial ²²Na⁺ transport. Disruption of the Na/K-ATPase·c-Src signaling complex attenuated ouabain-stimulated protein carbonylation. Ouabain-stimulated protein carbonylation is reversed after removal of ouabain, and this reversibility is largely independent of de novo protein synthesis and degradation by either the lysosome or the proteasome pathways. Furthermore, …

Spinal Cord Injury And Autonomic Dysreflexia- A Case Report, Apurva Bhatt, Brit Moore, Talal Asif, Kristy E. Steigerwalt, Rebecca R. Pauly

Marshall Journal of Medicine

Autonomic dysreflexia (AD) is a life threatening condition affecting patients with spinal cord lesions T6 level and above. A 51 year old male with a history of paraplegia due to a C6 spinal cord injury (30 years prior) presented with recurrent debilitating episodic diaphoresis, hypertension, low body temperature, and bradycardia. Previous hospitalizations presumed sepsis from UTI to be the etiology, however on further evaluation his symptoms were consistent with undiagnosed AD. This article describes a unique case presentation and reviews AD in depth, including the etiology, pathophysiology and management.

Why Does Obesity Lead To Hypertension? Further Lessons From The Intersalt Study., Preeya T. Shah, Anna P. Shapiro, Zeid Khitan Md, Prasanna Santhanam Md, Joseph I. Shapiro Md

Joseph I Shapiro MD

Objectives To analyze correlations between major determinants of blood pressure (BP), in efforts to generate and compare predictive models that explain for variance in systolic, diastolic, and mean BP amongst participants of the Intersalt study. Methods Data from the Intersalt study, consisting of nearly 10,000 subjects from 32 different countries, were reviewed and analyzed. Published mean values of 24 hour urinary electrolyte excretion (Na+, K+), 24 hour urine creatinine excretion, body mass index (BMI, kg/m^2), and blood pressure data were extracted and imported into Matlab™ for stepwise linear regression analysis. Results As shown earlier, strong correlations between urinary sodium excretion …

Na/K-Atpase Amplification Of Oxidant Stress; A Universal But Unrecognized Clinical Target?, Zijian Xie, Phd, Joseph I. Shapiro, Md

Joseph I Shapiro MD

The Na/K-ATPase has a signaling function which appears to be separate from its ion pumping function. This signaling function refers to the transduction of conformational changes in the Na/K-ATPase alpha1 subunit into activating Src’s tyrosine kinase activity, triggering a cascade which generates reactive oxygen species (ROS), modulates other signaling pathways, and causes many physiological and pathophysiological effects. We have recently observed that ROS themselves as well as cardiotonic steroids can actually initiate the signal by directly inducing conformational changes in alpha1. It therefore appears that the Na/K-ATPase signal cascade can serve as a feed forward amplification for ROS with circulating …

Why Does Obesity Lead To Hypertension? Further Lessons From The Intersalt Study., Preeya T. Shah, Anna P. Shapiro, Zeid Khitan Md, Prasanna Santhanam Md, Joseph I. Shapiro Md

Zeid J. Khitan

Objectives To analyze correlations between major determinants of blood pressure (BP), in efforts to generate and compare predictive models that explain for variance in systolic, diastolic, and mean BP amongst participants of the Intersalt study. Methods Data from the Intersalt study, consisting of nearly 10,000 subjects from 32 different countries, were reviewed and analyzed. Published mean values of 24 hour urinary electrolyte excretion (Na+, K+), 24 hour urine creatinine excretion, body mass index (BMI, kg/m^2), and blood pressure data were extracted and imported into Matlab™ for stepwise linear regression analysis. Results As shown earlier, strong correlations between urinary sodium excretion …

Upregulation Of Heme Oxygenase-1 Combined With Increased Adiponectin Lowers Blood Pressure In Diabetic Spontaneously Hypertensive Rats Through A Reduction In Endothelial Cell Dysfunction, Apoptosis And Oxidative Stress, Jian Cao, George Drummond, Kazuyoshi Inoue, Komal Sodhi, Xiao Ying Li, Shinji Omura

Komal Sodhi

This study was designed to investigate the effect of increased levels of HO-1 on hypertension exacerbated by diabetes. Diabetic spontaneously hypertensive rat (SHR) and WKY (control) animals were treated with streptozotocin (STZ) to induce diabetes and stannous chloride (SnCl2) to upregulate HO-1. Treatment with SnCl2 not only attenuated the increase of blood pressure (p<0.01), but also increased HO-1 protein content, HO activity and plasma adiponectin levels, decreased the levels of superoxide and 3-nitrotyrosine (NT), respectively. Reduction in oxidative stress resulted in the increased expression of Bcl-2 and AKT with a concomitant reduction in circulating endothelial cells (CEC) in the …

Role Of Dietary Components In Modulating Hypertension, Andrew Feyh, Lucas Bracero, Hari Vishal Lakhani, Prasanna Santhanam, Joseph I. Shapiro Md, Zeid Khitan Md, Komal Sodhi

Biochemistry and Microbiology

Hypertension is a major health issue, particularly in medically underserved populations that may suffer from poor health literacy, poverty, and limited access to healthcare resources. Management of the disease reduces the risk of adverse outcomes, such as cardiovascular or cerebrovascular events, vision impairment due to retinal damage, and renal failure. In addition to pharmacological therapy, lifestyle modifications such as diet and exercise are effective in managing hypertension. Current diet guidelines include the DASH diet, a low-fat and low-sodium diet that encourages high consumption of fruits and vegetables. While the diet is effective in controlling hypertension, adherence to the diet is …

Na/K-Atpase Amplification Of Oxidant Stress; A Universal But Unrecognized Clinical Target?, Zijian Xie, Phd, Joseph I. Shapiro, Md

Marshall Journal of Medicine

The Na/K-ATPase has a signaling function which appears to be separate from its ion pumping function. This signaling function refers to the transduction of conformational changes in the Na/K-ATPase alpha1 subunit into activating Src’s tyrosine kinase activity, triggering a cascade which generates reactive oxygen species (ROS), modulates other signaling pathways, and causes many physiological and pathophysiological effects. We have recently observed that ROS themselves as well as cardiotonic steroids can actually initiate the signal by directly inducing conformational changes in alpha1. It therefore appears that the Na/K-ATPase signal cascade can serve as a feed forward amplification for ROS with circulating …

Why Does Obesity Lead To Hypertension? Further Lessons From The Intersalt Study., Preeya T. Shah, Anna P. Shapiro, Zeid Khitan Md, Prasanna Santhanam Md, Joseph I. Shapiro Md

Marshall Journal of Medicine

Objectives

To analyze correlations between major determinants of blood pressure (BP), in efforts to generate and compare predictive models that explain for variance in systolic, diastolic, and mean BP amongst participants of the Intersalt study.

Methods

Data from the Intersalt study, consisting of nearly 10,000 subjects from 32 different countries, were reviewed and analyzed. Published mean values of 24 hour urinary electrolyte excretion (Na+, K+), 24 hour urine creatinine excretion, body mass index (BMI, kg/m^2), and blood pressure data were extracted and imported into Matlab™ for stepwise linear regression analysis.

Results

As shown earlier, strong correlations between urinary sodium excretion …

Adiposity Predicts Pulse Pressure In Subjects With Chronic Kidney Disease: Data From The Modification Of Diet In Renal Disease, Preeya T. Shah Phd, Rebecca Martin, Juan R. Sanabria, Zeid Khitan Md, Prasanna Santhanam, Komal Sodhi, Nader G. Abraham, Joseph I. Shapiro Md

Biochemistry and Microbiology

Obesity is a known risk factor for hypertension, but the mechanisms by which this occurs are still unclear. As the body mass index (BMI) is frequently used to define obesity, but the BMI does not distinguish between adipose and other tissues, we sought to develop another index of obesity. We decided to look at the ratio of BMI to urinary creatinine excretion as the latter measurement is believed to be an index of muscle mass. We used data from the modification of diet in renal disease (MDRD) study as urinary creatinine collections and blood pressure measurements were readily available in …

Cerebrovascular Risk Factors, Arteriolar Sclerosis, And Cognitive Decline In The Kentucky Appalachian “Stroke-Belt”, Omar M. Al-Janabi

Theses and Dissertations--Medical Sciences

The relationship between cerebrovascular disease (CVD) risk factors and cognitive impairment or dementia has been widely studied with significant variability in findings between groups. We hypothesized that chronic small vessel injury in the form of arteriolar sclerosis, measured quantitatively using MRI to measure total white matter hyperintensity (WMH) volumes, would identify specific association of CVD risk factors and patterns of cognitive decline, associated with mild cognitive impairment of the cerebrovascular type, that represent the core features of vascular cognitive impairment in our cohort.

A Cross-sectional analysis of clinical and quantitative MRI data on 114 subjects with normal cognitive function (n=52) …

The Relation Between Serum Cathepsin D Level And Carotid Intima-Media Thickness In Nondiabetic Hypertensive Patients, Ni̇hal Özkayar, Fatma Akyel, Ayşe Nurdan Barça, Serhan Vahi̇t Pi̇şki̇npaşa, Turan Turhan, İhsan Ateş, Fati̇h Dede

Turkish Journal of Medical Sciences

Background/aim: We aimed to investigate the relation between carotid intima-media thickness (CIMT) and serum cathepsin D level in hypertensive patients. Materials and methods: This was a cross-sectional study of 74 hypertensive patients (22 males and 52 females, with a mean age of 51.86 ± 11.75 years). Serum levels of cathepsin D were measured with an enzyme-linked immunosorbent assay. CIMT measurements were taken from 3 different points: right and left common carotid arteries, bifurcation, and the first 2 cm of the internal carotid artery. Mean CIMT was calculated by averaging the measurements taken 3 times from each carotid artery. Results: Mean …

Effects Of Blood Pressure And Sex On Heart-Vessel Coupling In Essential Hypertension, Changjuan Hao, Chunsong Kang, Jiping Xue, Kailing Shi, Hong Lv, Zhaojun Li

Turkish Journal of Medical Sciences

Background/aim: This study aimed to investigate the impact of blood pressure and sex on heart-vessel coupling in patients with essential hypertension via ultrasound. Materials and methods: We studied 76 patients with essential hypertension (48 males and 28 females) and 65 healthy controls (33 males and 32 females). Coupling parameters were obtained using ultrasound technology combined with brachial artery blood pressure measurement. Results: The Ea and Ees were higher in the hypertension group than in the control group (P < 0.01), with no statistically significant difference in Ea/Ees between the two groups (P >0.05). After subjects were classified by sex, the Ea and Ees of males and females in the hypertension group were higher than …

The Effects Of Novokinin, An At2 Agonist, On Blood Pressure, Vascular Responses, And Levels Of Adma, Nadph Oxidase, And Rho Kinase In Hypertension Induced By Nos Inhibition And Salt, Emre Mutlu, Selçuk İlhan, Eli̇f Onat, Murat Kara, Engi̇n Şahna

Turkish Journal of Medical Sciences

Background/aim: The effects of AT2 receptor agonist novokinin on blood pressure, eNOS, NADPH oxidase, protein arginine methyltransferases (PRMTs), and Rho kinase in hypertension were investigated. Furthermore, in isolated thoracic aorta rings, contractile and dilator responses were studied. Materials and methods: To develop hypertension, L-NAME was administered intraperitoneally and salt was given with tap water (1%) for 4 weeks. Novokinin was administered intraperitoneally for the last 2 weeks. Blood pressures were measured using the tail-cuff method and enzyme levels by real-time polymerase chain reaction in aortic tissues. Results: Blood pressure increased significantly in hypertensive rats. Novokinin reduced the blood pressure in …