Physiology Commons^™

Over-Expression Of Copper/Zinc Superoxide Dismutase In The Median Preoptic Nucleus Attenuates Chronic Angiotensin Ii-Induced Hypertension In The Rat., John P. Collister, Mitch Bellrichard, Donna Drebes, David Nahey, Jun Tian, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

The brain senses circulating levels of angiotensin II (AngII) via circumventricular organs, such as the subfornical organ (SFO), and is thought to adjust sympathetic nervous system output accordingly via this neuro-hormonal communication. However, the cellular signaling mechanisms involved in these communications remain to be fully understood. Previous lesion studies of either the SFO, or the downstream median preoptic nucleus (MnPO) have shown a diminution of the hypertensive effects of chronic AngII, without providing a clear explanation as to the intracellular signaling pathway(s) involved. Additional studies have reported that over-expressing copper/zinc superoxide dismutase (CuZnSOD), an intracellular superoxide (O2·-) scavenging enzyme, in …

The Effect Of Maternal Aldosterone Levels On The Expression Of 11b-Hsd Isoenzymes In Normal And Hypertensive Rat Placentae, Nicole Jorissen

Journal of Undergraduate Research at Minnesota State University, Mankato

In this project, we developed a Western blotting procedure to semi-quantitate levels of 11β-HSD1 and 11β-HSD2 in whole cell extracts. Then, we applied this technique to analyze the effect of reduced maternal aldosterone levels on the expression of 11β-HSD1 and 11β-HSD2 isoenzymes in the placental tissue in both normal and hypertensive rats. These enzymes control levels of glucocorticoids which compete for aldosterone’s mineralocorticoid receptor. Overstimulation of this receptor results in hypertension. If aldosterone levels decrease, levels of the enzymes controlling active glucocorticoid concentrations might change to compensate for the lowered aldosterone levels. Decreased placental 11β-HSD2 expression could affect hypertension in …

Muscle Metaboreflex Control Of Cardiovascular Function In Hypertension, Marty Daniel Spranger

Wayne State University Dissertations

Skeletal muscle ischemia during or immediately following exercise leads to the accumulation of metabolites (e.g., lactate, proton and diprotonated phosphate) which activate chemoreceptive afferents within the muscle leading to a reflex increase in sympathetic outflow generating substantial increases in mean arterial pressure (MAP), cardiac output (CO) and heart rate (HR) - termed the muscle metaboreflex. When the reflex is activated during submaximal dynamic exercise, the pressor response occurs via increased CO with no net peripheral vasoconstriction. When metaboreflex activation is sustained during the recovery from exercise (i.e., post-exercise muscle ischemia - (PEMI)), whereas MAP remains elevated for as long as …

Renal Humoral, Genetic And Genomic Mechanisms Underlying Spontaneous Hypertension, Jason A. Collett

Theses and Dissertations--Biology

In spite of significant progress in our knowledge of mechanisms that control blood pressure, our understanding of the pathogenesis of hypertension, its genetics, and population efforts to control blood pressure, hypertension remains the leading risk factor for mortality worldwide. It’s estimated that 1 out of every 3 adults has hypertension. Hypertension is a major risk factor for cardiovascular disease and stroke, and is considered a primary or contributing cause of death to more than 2.4 million US deaths each year. Although spontaneous hypertension has been the subject of substantial research, many critical questions remain unanswered.

To investigate mechanisms underlying spontaneous …

An Analysis Of Abnormal Electrocardiograms In First And Second Year Medical School Students, Molly Anne Kalish

PCOM Biomedical Studies Student Scholarship

The high stress level placed upon medical school students, particularly during their first and second didactic years, may have a negative effect on their health. Although surveys and subjective questionnaires have been used to evaluate the effects medical school has upon a student’s cardiovascular health, there has been little clinical data obtained to confirm this notion. The aim of this longitudinal study was to demonstrate whether any abnormal cardiovascular parameters, specifically QTc wave interval, cardiac axis vector and blood pressure abnormalities, could be documented to occur in two different classes of medical students during their first two years. Such information …

Aquatic Treadmill Training Reduces Blood Pressure Reactivity To Acute Graded Exercise In Previously Sedentary Adults, Brad S. Lambert, Nicholas P. Greene, Dustin P. Joubert, Steven E. Riechman, James D. Fluckey, Stephen F. Crouse, Alex T. Carradine

International Journal of Exercise Science: Conference Proceedings

Endurance exercise may reduce blood pressure and improve vasodilatory capacity thereby blunting the hypertensive response to stress. To test the efficacy of a novel model of low-impact endurance training, the aquatic-based treadmill (ATM), to improve blood pressure parameters, we recruited 60 sedentary adults and randomized to 12-weeks of either ATM (n = 36 [19 men, 17 women] , 41±2 yr, 173.58 ±1.58cm, 93.19 ±3.15kg) or land-based treadmill (LTM, n = 24 [11 men, 13 women], 42 ±2yr, 170.39 ±1.94cm, 88.14 ±3.6kg) training; 3sessions·wk-1, progressing to 500 kcal·session-1, 85% VO2max. The maximal Bruce treadmill test protocol was performed before and after …

Thick Ascending Limb Nitric Oxide Production And Inhibition Of Nkcc2 Activity Are Impaired In Angiotensin Ii-Induced Hypertension, Vanesa Daniela Ramseyer

Wayne State University Dissertations

Cardiovascular disease is the leading cause of death in the US. Hypertension, which affects about 30 % of the US population, is an important risk factor in the development of this disease. Inappropriately elevated sodium reabsorption by the kidney contributes to hypertension; therefore, studying the mechanisms that lead to enhanced sodium transport is important in understanding this pathology. The thick ascending limb (THAL) reabsorbs 30% of the filtered sodium chloride load. Nitric oxide (NO) produced by NO synthase type 3 (NOS3) increases cyclic GMP (cGMP) and inhibits THAL transport by reducing Na/K/2Cl cotransporter type 2 (NKCC2) activity. Interestingly, in angiotensin …

Osteoblast Activity Is Diminished In Young Spontaneously Hypertensive Rats, Tyler J. Benson, Brandon Cherry, Steve Mifflin, Rhonda Prisby

International Journal of Exercise Science: Conference Proceedings

Spontaneously Hypertensive Rats (SHR) are used as a genetic model of essential hypertension. Reductions in cortical and cancellous bone mass and increased bone turnover have been observed in aged SHR vs. Wistar-Kyoto (WKY) rats, normotensive genetics controls. In addition, antihypertensive aids have been effective in improving bone parameters in hypertensive rats. Thus, the relation between hypertension and bone remodeling warrants further attention. The purpose of this study was to determine how acute (i.e., 9 weeks) hypertension effects bone remodeling parameters (i.e., osteoclast and osteoblast activity). Methods: Right femora from 14-week-old SHR (n=5) and WKY (n=4) rats were dissected, fixed in …

Ipla2Β Overexpression In Smooth Muscle Exacerbates Angiotensin Ii-Induced Hypertension And Vascular Remodeling, Lindsay E Calderon, Shu Liu, Wen Su, Zhongwen Xie, Zhenheng Guo, Wanda Eberhard, Ming C. Gong

Physiology Faculty Publications

OBJECTIVES: Calcium independent group VIA phospholipase A₂ (iPLA₂β) is up-regulated in vascular smooth muscle cells in some diseases, but whether the up-regulated iPLA₂β affects vascular morphology and blood pressure is unknown. The current study addresses this question by evaluating the basal- and angiotensin II infusion-induced vascular remodeling and hypertension in smooth muscle specific iPLA₂β transgenic (iPLA₂β-Tg) mice.

METHOD AND RESULTS: Blood pressure was monitored by radiotelemetry and vascular remodeling was assessed by morphologic analysis. We found that the angiotensin II-induced increase in diastolic pressure was significantly higher in iPLA₂β-Tg …

Spatial Distribution And Modulation Of Nitric Oxide Synthase In A Hypertensive Rat Model, Andrew Yannaccone

Theses and Dissertations

There are gaps in the fundamental understanding of the expression of nitric oxide synthases (NOS) in the microvasculature. We examined co-localization of NOS1 (nNOS), NOS2 (iNOS) and NOS3 (eNOS) in the spinotrapezius muscle of young adult male Wistar-Kyoto (WKY) and Spontaneously Hypertensive (SHR) rats according to fiber type using immunohistochemistry and brightfield microscopy. Data regarding fiber distribution, population and morphology data were collected. Alkaline phosphatase staining was used to determine capillary density and average number of capillaries around a fiber. Gel electrophoresis and Western blot techniques were used to compare myosin heavy chain (MHC) protein expression with fiber type population …

The Effect Of Exercise On Endothelin And Endothelin Receptor Levels In Shr And Wky Male And Female Rats, Lacey Stiller

All Graduate Theses, Dissertations, and Other Capstone Projects

The role of exercise as a means to modulate renal function in hypertension is unclear. However, prior studies in the laboratory of Dr. Penny Knoblich indicate that exercised female spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats excrete significantly more sodium in response to a rise in blood pressure relative to exercised male and sedentary female SHR and WKY rats. The purpose of this study was to evaluate the effects of exercise on endothelin and endothelin receptor levels in the urine and kidneys of male and female SHR and WKY rats, to elucidate potential mechanisms to explain an increase …

Age-Associated Disruption Of Molecular Clock Expression In Skeletal Muscle Of The Spontaneously Hypertensive Rat, Mitsunori Miyazaki, Elizabeth Schroder, Stephanie E. Edelmann, Michael E. Hughes, Karl Kornacker, C. William Balke, Karyn A. Esser

Physiology Faculty Publications

It is well known that spontaneously hypertensive rats (SHR) develop muscle pathologies with hypertension and heart failure, though the mechanism remains poorly understood. Woon et al. (2007) linked the circadian clock gene Bmal1 to hypertension and metabolic dysfunction in the SHR. Building on these findings, we compared the expression pattern of several core-clock genes in the gastrocnemius muscle of aged SHR (80 weeks; overt heart failure) compared to aged-matched control WKY strain. Heart failure was associated with marked effects on the expression of Bmal1, Clock and Rora in addition to several non-circadian genes important in regulating skeletal muscle phenotype including …

Mechanisms Of Prenatal High-Salt "Fetal Programming" Resulting In Stress Hyperresponsiveness In The Adult Female Offspring In The Sprague Dawley Rat., Clinton L. Johnson

Theses and Dissertations

Female offspring of Sprague-Dawley rats fed a high-salt diet (HS) during pregnancy show an enhancement of mean arterial pressure (MAP) and heart rate (HR) response to acute stress in adulthood compared to offspring whose mothers were fed a normal-salt diet (NS) [1]. In the present study, we first examined the expression of soluble epoxide hydrolase (SEH) protein in brain tissue. Whole brains were collected and SEH gene (EPHX2) mRNA and SEH protein expression were analyzed using RT-PCR and Western blot, respectively. mRNA levels were relatively decreased in high-salt rats (1.0 ± 0.32 NS vs 0.39 ± 0.07 HS, n=6). However, …

Role Of Neutrophils In Enhancing Vascular Reactivity To Angiotensin Ii In Preeclampsia, Nikita Mishra

Theses and Dissertations

Women with preeclampsia have enhanced vascular reactivity to Angiotensin II (Ang II) and extensive vascular infiltration of neutrophils. The primary mechanism to enhance vessel reactivity is RhoA kinase that phosphorylates MYPT1 to inhibit myosin light chain (MLC) phosphatase. Therefore, MLCs remain phosphorylated and increase sensitivity to calcium. Neutrophils release reactive oxygen species (ROS), which can activate this pathway, so we hypothesized that neutrophils would enhance vessel reactivity to Ang II. Omental vessels from normal pregnant women were used to study vascular reactivity. Ang II dose response (0.001-10µM) was significantly enhanced with perfusion of neutrophils (<2000/mm3, activated with IL-8) or ROS. Addition of superoxide dismutase (SOD)/Catalase to quench ROS or 3µM Y-27632, a specific RhoA kinase inhibitor, blocked enhancement. Vascular smooth muscle expression of pMYPT1 and pMLC in cell culture was significantly increased by neutrophils or ROS. The increase was prevented by Y-27632. RhoA kinase activity assay showed a 3-fold increase in RhoA kinase activity in omental vessels treated with ROS. Similarly, ROS also enhanced vessel reactivity to another vasoconstrictor, norepinephrine, via RhoA kinase. In preeclamptic women, increased neutrophil infiltration is associated with increased vascular expression and production of matrix metalloproteinase-1 (MMP-1). MMP-1 activates protease activated receptor-1 (PAR-1), which could cause endothelial endothelin-1 release, so we considered a novel hypothesis that MMP-1 might cause vasoconstriction and enhance vessel reactivity to Ang II via PAR-1. Omental vessels perfused with activated MMP-1 (0.025-25ng/ml) showed dose-dependent vasoconstriction. Perfusion of activated MMP-1 (2.5ng/ml) significantly enhanced dose response to angiotensin II. MMP-1 mediated vasoconstriction and enhanced vessel reactivity to Ang II was abolished by co-perfusion of 10µM SCH-79797, a specific PAR-1 blocker, and by 5µM BQ-123, a specific endothelin-1 type A receptor blocker. These data are the first to show that activated neutrophils enhance vascular reactivity to Ang II via ROS and the RhoA kinase pathway. They are also the first to show that MMP-1 induces vasoconstriction and enhances vessel reactivity to Ang II. Thus, vascular neutrophil infiltration leading to ROS and MMP-1 generation could be an important mechanism for hypertension in preeclampsia.

Mechanisms Of Regulation Of Proximal Tubule Sodium Transporters In Obesity-Induced Hypertension, Marta A. Ambrozewicz

Theses and Dissertations in Biomedical Sciences

Hypertension is one of the common complications of obesity. Using a rat model of diet induced obesity and hypertension we investigated some of the mechanisms that are involved in regulation of blood pressure in obesity. The first aim of this study was to determine the role of proximal tubule transporters on the renal sodium handling in obese hypertensive (OP) and lean normotensive (OR) rats. An acute increase in renal perfusion pressure resulted in a blunted natriuretic response in OP vs. OR rats and indicated that increased sodium reabsorption in the proximal tubule is casual, at least in part, for hypertension …

Y27632, A Rho-Activated Kinase Inhibitor, Normalizes Dysregulation In Alpha1-Adrenergic Receptor-Induced Contraction Of Lyon Hypertensive Rat Artery Smooth Muscle., Maria Regina Freitas, Masumi Eto, Jason A Kirkbride, Christa Schott, Jean Sassard, Jean-Claude Stoclet

Department of Molecular Physiology and Biophysics Faculty Papers

RhoA-activated kinase (ROK) is involved in the disorders of smooth muscle contraction found in hypertension model animals and patients. We examined whether the alpha1-adrenergic receptor agonist-induced ROK signal is perturbed in resistance small mesentery artery (SMA) of Lyon genetically hypertensive (LH) rats, using a ROK antagonist, Y27632. Smooth muscle strips of SMA and aorta were isolated from LH and Lyon normotensive (LN) rats. After Ca(2+)-depletion and pre-treatment with phenylephrine (PE), smooth muscle contraction was induced by serial additions of CaCl(2). In LH SMA Ca(2+) permeated cells to a lesser extent as compared with LN SMA, while CaCl(2)-induced contraction of LH …

The Increase In Renal Sodium Excretion In Response To Angiotensin Ii Infusion In Exercised Female Rats Is Dependent On A Rise In Renal Perfusion Pressure, Karmon Janssen

All Graduate Theses, Dissertations, and Other Capstone Projects

Prior studies in this lab have shown that chronically exercised female spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats excrete a greater amount of sodium in response to angiotensin II (Ang II) infusion than do sedentary rats. The current study determined if the difference in renal sodium excretion persisted when the renal perfusion pressure (RPP) was held constant. Female SHR and female WKY rats were separated into sedentary and exercised groups at 4 weeks of age. The exercise group voluntarily exercised for at least eight weeks using an exercise wheel and time/distance monitor. At 13 weeks of age or older, …

Maternal High-Salt Diet During Pregnancy In Sprague Dawley Rats Programs Exaggerated Stress-Induced Blood Pressure And Heart Rate Responses In Adult Female Offspring, Summer Hayes King

Theses and Dissertations

The prenatal environment has been shown to have lasting effects on cardiovascular health. In the present study, pregnant rats were fed a 0.7% NaCl normal salt (NS) diet or an 8% NaCl high salt (HS) diet throughout pregnancy. Adult offspring were fitted with radiotelemetry probes to continuously measure blood pressure and heart rate. Rats were placed in restraining cages to test for a programmed acute stress hyperresponsiveness. Offspring were challenged with HS diet for one week to determine if blood pressure salt sensitivity had been programmed by the prenatal HS diet. Animals were killed following resting and acute stress conditions, …

The Expression Of Neutrophil Products, Myeloperoxidase And Matrix Metalloproteinase 8, In Systemic Vasculature Of Obese And Preeclamptic Women, Juhi Shukla

Theses and Dissertations

Evidence shows the activation of neutrophils in the systemic vasculature of obese and preeclamptic women. In this study, I evaluated whether expression of neutrophil products, myeloperoxidase (MPO) and matrix metalloproteinase 8 (MMPS), was associated with neutrophil infiltration in systemic vascular tissue of obese and preeclamptic women. I tested my hypotheses by using immunohistochemical studies to look at the expression of MPO and MMP8 in the vasculature of obese and preeclamptic women. There was a significantly greater expression of MPO and MMP8 in the vasculature of preeclamptic women as compared to normal pregnant and normalnonpregnant women. The vasculature of obese women …