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Published on: November 7, 2017
Enhanced atherosclerosis and kidney dysfunction in eNOS(-/-)Apoe(-/-) mice are ameliorated by enalapril treatment
J W Knowles1, R L Reddick, J C Jennette
1Department of Pathology, Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Abstract:
Hypertension and atherosclerosis are each important causes of morbidity and mortality in the developed world. We have investigated the interaction between these conditions by breeding mice that are atherosclerotic due to lack of apolipoprotein (apo) E with mice that are hypertensive due to lack of endothelial nitric oxide synthase (eNOS). The doubly deficient mice (nnee) have higher blood pressure (BP) and increased atherosclerotic lesion size but no change in plasma lipoprotein profiles compared with normotensive but atherosclerotic (NNee) mice. The nnee mice also develop kidney damage, evidenced by increased plasma creatinine, decreased kidney weight/body weight ratio, and glomerular lipid deposition and calcification. Enalapril treatment abolishes the deleterious effects of eNOS deficiency on BP, atherosclerosis, and kidney dysfunction in nnee mice. In striking contrast, a genetic lack of inducible NOS, which does not affect BP, has no effect on the development of atherosclerotic lesions in Apoe(-/-) mice. We also observed a positive relationship between BP and size of atherosclerotic lesions These results suggest that the atherogenic effects of eNOS deficiency can be partially explained by an increase in BP and reemphasize the importance of controlling hypertension in preventing atherosclerosis.
Insights
Mice lacking endothelial nitric oxide synthase (eNOS) and apolipoprotein E developed hypertension, atherosclerosis, and kidney damage. Enalapril treatment improved these conditions, highlighting hypertension
Area of Science:
- Cardiovascular Science
- Nephrology
- Molecular Biology
Background:
- Hypertension and atherosclerosis are leading causes of morbidity and mortality.
- Endothelial nitric oxide synthase (eNOS) plays a crucial role in cardiovascular health.
- Apolipoprotein E (ApoE) deficiency is a common model for studying atherosclerosis.
Purpose of the Study:
- To investigate the interaction between hypertension and atherosclerosis.
- To determine the role of eNOS in the development of atherosclerosis and kidney damage in the context of hypertension.
- To evaluate the therapeutic effect of enalapril on these conditions.
Main Methods:
- Breeding of doubly deficient mice (apoE-/- and eNOS-/-).
- Assessment of blood pressure, atherosclerotic lesion size, plasma creatinine, and kidney pathology.
- Treatment with enalapril and comparison with inducible NOS (iNOS) deficient mice.
Main Results:
- Doubly deficient mice (nnee) exhibited higher blood pressure and increased atherosclerotic lesion size compared to controls.
- nnee mice showed signs of kidney damage, including elevated plasma creatinine and glomerular lipid deposition.
- Enalapril treatment ameliorated hypertension, atherosclerosis, and kidney dysfunction in nnee mice.
- Genetic deficiency of iNOS did not affect atherosclerotic lesion size in Apoe(-/-) mice.
Conclusions:
- eNOS deficiency exacerbates atherosclerosis and causes kidney damage, partly due to increased blood pressure.
- Controlling hypertension is critical for preventing atherosclerosis.
- Enalapril is a potential therapeutic agent for managing hypertension-related cardiovascular and renal complications.
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