Endocrine Abstracts

Context: Glucocorticoids have adverse systemic effects which may predispose to cardiovascular disease. The effect of glucocorticoid use on cardiovascular disease has not been assessed.Objective: To test the hypothesis that users of exogenous glucocorticoids have a dose-dependent increased risk of cardiovascular disease; in particular, that supraphysiological doses will be associated with cardiovascular disease.Design: A cohort study using a record linkage database....

Objective. The aims of our study were to utilise a combination of high fidelity phenotyping, microarray gene expression profiling and conserved synteny mapping between rodent and human genomes to identify genetic determinants underlying human hypertension.Methods. We used the stroke-prone spontaneously hypertensive rat (SHRSP) and a congenic strain (SP.WKYGla2c*) produced by introgressing a quantitative trait locus responsible for blood pressure regulation on rat chromosom...

Objective: The spontaneously hypertensive stroke prone rat (SHRSP) is a model of insulin resistance and dyslipidemia. Feeding a 60% fructose diet exaggerates these phenotypes. The Y chromosome may influence lipid levels in the spontaneously hypertensive rat (SHR). Therefore we aim to characterise the metabolic syndrome using in vivo and dyslipidemic phenotpyes in the SHRSP and examine the contribution of the Y chromosome.Methods: SHRSP and WKY Y consomic strains (SP...

Regulation of the epithelial sodium channel (ENaC) trafficking in cells of the distal nephron is of major importance in the control of sodium reabsorption. Mutations in the genes compromising the molecular pathway by which corticosteroids regulate ENaC sodium reabsorption cause several hypertensive syndromes in humans. The molecular events underpinning ENaC exo- and endocytosis and the hormonal effects on ENaC trafficking are poorly understood. To start elucidating these pathw...

Testosterone therapy has been shown to benefit men with heart failure or coronary artery disease, an activity proposed to be mediated via its vasodilatory efficacy. Testosterone has been demonstrated to dilate human coronary arteries, but it is unknown whether testosterone has a similar action in human pulmonary or systemic vessels.Male patients were recruited from cardiothoracic (n = 14, age = 68 plus/minus 9) or gastrointestinal (n = 8, age = 70 plus/minus 3) operating l...

Increased superoxide(SO) production reduces nitric oxide(NO) bioactivity and increases oxidative stress contributing to endothelial dysfunction in vascular disease. The gene coding for p22phox, a critical component of the NADH/NAD(P)H oxidase enzyme system which produces vascular SO, is CYBA. Among the allelic polymorphisms reported in CYBA is C242T which is associated with progression of coronary atherosclerosis. Radial applanation tonometry with pulse waveform analysis (PWA)...

Previously we reported two loss-of-function dominant negative mutations (P467L, V290M) in human peroxisome proliferator-activated receptor gamma (PPARg) in three individuals with severe insulin resistance, early onset type 2 diabetes mellitus (T2DM) and hypertension. Subsequent detailed clinical and radiological evaluation of these subjects has revealed that each exhibits a stereotyped pattern of partial lipodystrophy affecting the limbs and buttocks. Recently a female with pa...

Glucocorticoid receptor (GR) splicing may influence glucocorticoid sensitivity. We aimed to identify GR isoforms in the lung by using immunohistochemistry, immunoblotting, co-immunoprecipitation western and RT-PCR approaches.The distribution of GR protein in rat lung was different when we used an N terminal antibody (M20) compared to a C terminal antibody (GRalpha). M20 detected diffuse expression in all cell types and higher expression in the epithelium. In contrast GRalp...