Endocrinology publications (MU)
https://hdl.handle.net/10355/8497
The items in this collection are the scholarly output of the faculty, staff, and students of the <i>Division of Endocrinology</i>.2024-03-29T11:07:39ZMineralocorticoid Receptor Blockade Attenuates Chronic Overexpression of the Renin-Angiotensin- Aldosterone System Stimulation of Reduced Nicotinamide Adenine Dinucleotide Phosphate Oxidase and Cardiac Remodeling
https://hdl.handle.net/10355/8499
Mineralocorticoid Receptor Blockade Attenuates Chronic Overexpression of the Renin-Angiotensin- Aldosterone System Stimulation of Reduced Nicotinamide Adenine Dinucleotide Phosphate Oxidase and Cardiac Remodeling
Stas, Sameer; Whaley-Connell, Adam T.; Habibi, Javad, 1947-; Appesh, Lama; Hayden, Melvin; Karuparthi, Poorna R.; Qazi, Mahnaz; Morris, E. Matthew; Cooper, Shawna A.; Link, C. Daniel; Stump, Craig; Hay, Meredith; Ferrario, Carlos M.; Sowers, James R. (James Russell), 1942-
The renin-angiotensin-aldosterone system contributes to cardiac remodeling, hypertrophy, and left ventricular dysfunction.
Angiotensin II and aldosterone (corticosterone in rodents) together generate reactive oxygen species (ROS) via reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which likely facilitate this hypertrophy and remodeling. This investigation sought to determine whether cardiac oxidative stress and cellular remodeling could be attenuated by in vivo mineralocorticoid receptor (MR) blockade in a rodent model of the chronically elevated
tissue renin-angiotensin-aldosterone system, the transgenic TG (mRen2) 27 rat (Ren2). The Ren2 overexpresses the mouse renin transgene with resultant hypertension, insulin resistance, proteinuria, and cardiovascular damage. Young (6- to 7-wk-old) male Ren2 and age-matched Sprague-Dawley rats were treated with spironolactone or placebo for 3 wk. Heart
tissue ROS, immunohistochemical analysis of 3-nitrotyrosine,and NADPH oxidase (NOX) subunits (gp91phox recently renamed
NOX2, p22phox, Rac1, NOX1, and NOX4) were measured. Structural changes were assessed with cine-magnetic resonance
imaging, transmission electron microscopy, and light microscopy. Significant increases in Ren2 septal wall thickness (cine-magnetic resonance imaging) were accompanied by perivascular fibrosis, increased mitochondria, and other ultrastructural changes visible by light microscopy and transmission electron microscopy. Although there was no significant
reduction in systolic blood pressure, significant improvements were seen with MR blockade on ROS formation and NOX subunits (each P < 0.05). Collectively, these data suggest that MR blockade, independent of systolic blood pressure reduction, improves cardiac oxidative stress-induced structural
and functional changes, which are driven, in part, by angiotensin type 1 receptor-mediated increases in NOX.
doi: 10.1210/en.2006-1691
2007-08-01T00:00:00ZUltrastructural Islet Study of Early Fibrosis in the Ren2 Rat Model of Hypertension Emerging Role of the Islet Pancreatic Pericyte-Stellate Cell
https://hdl.handle.net/10355/8498
Ultrastructural Islet Study of Early Fibrosis in the Ren2 Rat Model of Hypertension Emerging Role of the Islet Pancreatic Pericyte-Stellate Cell
Hayden, Melvin; Karuparthi, Poorna R.; Habibi, Javad, 1947-; Wasekar, Chetan; Lastra, Guido; Manrique, Camilla; Stas, Sameer; Sowers, James R. (James Russell), 1942-
Type 2 diabetes mellitus is a multifactorial disease with polygenic and environmental stressors resulting in multiple metabolic toxicities and islet oxidative stress. We have integrated the role of the islet renin-angiotensin system (RAS) in the pathogenesis of early islet fibrosis utilizing the transgenic (mRen2)27 rodent model of hypertension and tissue RAS overexpression. The Ren2 pancreatic islet tissue was evaluated with transmission electron microscopy to study both early cellular and extracellular matrix remodeling. Major remodeling differences in the Ren2 model were found to be located within the islet exocrine interface, including deposition of early fibrillar-banded collagen (fibrosis) and cellular remodeling of the pericyte suggesting proliferation, migration, hypertrophy and activation as compared to the Sprague Dawley controls.
2007-01-01T00:00:00Z