Endothelial Mineralocorticoid Receptor Ablation Confers Protection Towards Endothelial Dysfunction in Experimental Diabetes in Mice

2021 ◽  
Author(s):  
Kristina S. Lyngsø ◽  
Boye L. Jensen ◽  
Pernille B. L. Hansen ◽  
Henrik Dimke
Keyword(s):  
Endothelial Dysfunction ◽  
Mineralocorticoid Receptor ◽  
Experimental Diabetes ◽  
Diabetes In Mice

Endothelial dysfunction and arterial pressure regulation during early diabetes in mice: roles for nitric oxide and endothelium-derived hyperpolarizing factor

2007 ◽  
Vol 293 (2) ◽  
pp. R707-R713 ◽  
Author(s):  
Sharyn M. Fitzgerald ◽  
Barbara K. Kemp-Harper ◽  
Helena C. Parkington ◽  
Geoffrey A. Head ◽  
Roger G. Evans
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Arterial Pressure ◽  
Early Stage ◽  
Mesenteric Arteries ◽  
No Production ◽  
Wild Type ◽  
Early Diabetes ◽  
Diabetes In Mice ◽  
Vehicle Treatment

We determined whether nitric oxide (NO) counters the development of hypertension at the onset of diabetes in mice, whether this is dependent on endothelial NO synthase (eNOS), and whether non-NO endothelium-dependent vasodilator mechanisms are altered in diabetes in mice. Male mice were instrumented for chronic measurement of mean arterial pressure (MAP). In wild-type mice, MAP was greater after 5 wk of Nω-nitro-l-arginine methyl ester (l-NAME; 100 mg·kg−1·day−1 in drinking water; 97 ± 3 mmHg) than after vehicle treatment (88 ± 3 mmHg). MAP was also elevated in eNOS null mice (113 ± 4 mmHg). Seven days after streptozotocin treatment (200 mg/kg iv) MAP was further increased in l-NAME-treated mice (108 ± 5 mmHg) but not in vehicle-treated mice (88 ± 3 mmHg) nor eNOS null mice (104 ± 3 mmHg). In wild-type mice, maximal vasorelaxation of mesenteric arteries to acetylcholine was not altered by chronic l-NAME or induction of diabetes but was reduced by 42 ± 6% in l-NAME-treated diabetic mice. Furthermore, the relative roles of NO and endothelium-derived hyperpolarizing factor (EDHF) in acetylcholine-induced vasorelaxation were altered; the EDHF component was enhanced by l-NAME and blunted by diabetes. These data suggest that NO protects against the development of hypertension during early-stage diabetes in mice, even in the absence of eNOS. Furthermore, in mesenteric arteries, diabetes is associated with reduced EDHF function, with an apparent compensatory increase in NO function. Thus, prior inhibition of NOS results in endothelial dysfunction in early diabetes, since the diabetes-induced reduction in EDHF function cannot be compensated by increases in NO production.

AUTONOMIC AND ENDOTHELIAL DYSFUNCTION IN EXPERIMENTAL DIABETES

2000 ◽  
Vol 22 (6) ◽  
pp. 623-634 ◽  
Author(s):  
B. Martínez-Nieves ◽  
H. L. Collins ◽  
S. E. DiCarlo
Keyword(s):  
Endothelial Dysfunction ◽  
Experimental Diabetes

Monoamine oxidases are novel sources of cardiovascular oxidative stress in experimental diabetes

2015 ◽  
Vol 93 (7) ◽  
pp. 555-561 ◽  
Author(s):  
Adrian Sturza ◽  
Oana M. Duicu ◽  
Adrian Vaduva ◽  
Maria D. Dănilă ◽  
Lavinia Noveanu ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Rat Model ◽  
Experimental Diabetes ◽  
Xylenol Orange ◽  
Diabetic Rat ◽  
Organ Bath ◽  
Monoamine Oxidases ◽  
Mao B ◽  
Cardiovascular Morbidity And Mortality ◽  
Endothelium Dependent Relaxation

Diabetes mellitus (DM) is widely recognized as the most severe metabolic disease associated with increased cardiovascular morbidity and mortality. The generation of reactive oxygen species (ROS) is a major event causally linked to the development of cardiovascular complications throughout the evolution of DM. Recently, monoamine oxidases (MAOs) at the outer mitochondrial membrane, with 2 isoforms, MAO-A and MAO-B, have emerged as novel sources of constant hydrogen peroxide (H2O2) production in the cardiovascular system via the oxidative deamination of biogenic amines and neurotransmitters. Whether MAOs are mediators of endothelial dysfunction in DM is unknown, and so we studied this in a streptozotocin-induced rat model of diabetes. MAO expression (mRNA and protein) was increased in both arterial samples and hearts isolated from the diabetic animals. Also, H2O2 production (ferrous oxidation – xylenol orange assay) in aortic samples was significantly increased, together with an impairment of endothelium-dependent relaxation (organ-bath studies). MAO inhibitors (clorgyline and selegiline) attenuated ROS production by 50% and partially normalized the endothelium-dependent relaxation in diseased vessels. In conclusion, MAOs, in particular the MAO-B isoform, are induced in aortas and hearts in the streptozotocin-induced diabetic rat model and contribute, via the generation of H2O2, to the endothelial dysfunction associated with experimental diabetes.

Abstract 096: Progesterone Upregulates Endothelial Mineralocorticoid Receptor Expression Which Predisposes Female Mice to Obesity-Induced Endothelial Dysfunction

Hypertension ◽  
2018 ◽  
Vol 72 (Suppl_1) ◽  
Author(s):  
Jessica L Faulkner ◽  
Simone Kennard ◽  
Galina Antonova ◽  
Zsolt Bagi ◽  
Iris Jaffe ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Mineralocorticoid Receptor ◽  
Receptor Expression ◽  
Female Mice

scholarly journals P172Monoamine oxidase inhibition corrects endothelial dysfunction in experimental diabetes

2014 ◽  
Vol 103 (suppl 1) ◽  
pp. S30.3-S30 ◽  
Author(s):  
A Sturza ◽  
L Noveanu ◽  
O Duicu ◽  
DM Muntean
Keyword(s):  
Endothelial Dysfunction ◽  
Experimental Diabetes ◽  
Oxidase Inhibition

Coronary endothelial dysfunction after cardiomyocyte-specific mineralocorticoid receptor overexpression

2011 ◽  
Vol 300 (6) ◽  
pp. H2035-H2043 ◽  
Author(s):  
Julie Favre ◽  
Ji Gao ◽  
An Di Zhang ◽  
Isabelle Remy-Jouet ◽  
Antoine Ouvrard-Pascaud ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Dysfunction ◽  
Nadph Oxidase ◽  
Coronary Arteries ◽  
Mineralocorticoid Receptor ◽  
Vascular Dysfunction ◽  
Reactive Oxygen ◽  
Oxidase Inhibitor ◽  
Oxygen Species ◽  
Coronary Endothelial Dysfunction

The deleterious effects of aldosterone excess demonstrated in cardiovascular diseases might be linked in part to coronary vascular dysfunction. However, whether such vascular dysfunction is a cause or a consequence of the changes occurring in the cardiomyocytes is unclear. Moreover, the possible link between mineralocorticoid receptor (MR)-mediated effects on the cardiomyocyte and the coronary arteries is unknown. Thus we used a mouse model with conditional, cardiomyocyte-specific overexpression of human MR (hMR) and observed the effects on endothelial function in isolated coronary segments. hMR overexpression decreased the nitric oxide (NO)-mediated relaxing responses to acetylcholine in coronary arteries (but not in peripheral arteries), and this was prevented by a 1-mo treatment either with an MR antagonist, vitamin E/vitamin C, or a NADPH oxidase inhibitor. hMR overexpression did not affect coronary endothelial NO synthase content nor its level of phosphorylation on serine 1177, but increased cardiac levels of reactive oxygen species, cardiac NADPH oxidase (NOX) activity, and expression of the NOX subunit gp91phox, which was limited to endothelial cells. Thus an increase in hMR activation, restricted to cardiomyocytes, is sufficient to induce a severe coronary endothelial dysfunction. We suggest a new paracrine mechanism by which cardiomyocytes trigger a NOX-dependent, reactive oxygen species-mediated coronary endothelial dysfunction.

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