Abstract
Background:Aldosterone plays a key role in the development of endothelial dysfunction and hypertension. The regulation of biogenesis and fusion/fission processes of vascular mitochondria has not been examined in aldosterone-induced hypertension. Thereby, we sought to explore in greater depth the role of aldosterone in mitochondrial biogenesis and fusion/fission processes in hypertension and the associated increases in oxidative stress.Methods:Male Wistar rats received aldosterone (1mg/Kg/day) + 1% NaCl as drinking water for 3 weeks.Results:Systolic blood pressure was elevated (p<0.05) in aldosterone-treated rats. eNOS and p-eNOSSer1177protein expression was down regulated (p<0.05) and NADPH oxidase subunit p22phox expression was increased (p<0.05) in aldosterone-treated rats. Expression of mitochondrial biogenesis proteins SIRT1, PGC1α, PPARγ, and TFAM decreased (p<0.05) in aldosterone-treated rats. Protein expression of vascular DRP1, OMA1 and S-OPA1 up regulated (p<0.05) in aldosterone-treated rats. MFN1 and L-OPA1 (p<0.05) decreased in aldosterone-treated animals.Conclusion:The results showed that, in aldosterone-treated rats, hypertension is likely associated with increased oxidative stress in the aorta and with changes in the regulation of two key mitochondrial processes such as biogenesis and fusion/fission processes. The overall mitochondrial alterations observed in the study may play a role in aldosterone-derived vascular oxidative stress and hypertension.
Highlights
Aldosterone mediates endothelial dysfunction and promotes hypertension [1 - 4]
The generation of ROS by aldosterone further leads to endothelial dysfunction decreasing endothelial nitric oxide synthase (eNOS) which is associated with hypertension [2, 5, 7]. eNOS plays an important role in mitochondria biogenesis and mitochondrial function [9, 38, 39]
Data in our study showed increased dynamin-related protein1 (DRP1) protein expression in the aorta of aldosterone-treated rats contributing to the role of mitochondrial fusion/fission processes alteration to hypertension via oxidative stress
Summary
Aldosterone mediates endothelial dysfunction and promotes hypertension [1 - 4]. Blockade of Mineralocorticoid Receptors (MR) prevents endothelial nitric oxide synthase (eNOS) downregulation associated with hypertension and heart failure in experimental studies [5 - 7]. The Open Hypertension Journal, 2018, Volume 10 77 angiotensin II (Ang II) receptor and/or mineralocorticoid receptor blockade, attenuates the mitochondrial abnormalities observed [10, 11]. These findings suggest a role of mitochondrial changes in cardiovascular alterations associated with RAAS impairment. The regulation of biogenesis and fusion/fission processes of vascular mitochondria has not been examined in aldosterone-induced hypertension. Thereby, we sought to explore in greater depth the role of aldosterone in mitochondrial biogenesis and fusion/fission processes in hypertension and the associated increases in oxidative stress
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call