Dahl Salt-Sensitive Rats Are Protected Against Vascular Defects Related to Diet-Induced Obesity
Open accessAbstract
Obesity increases plasma renin activity and angiotensin II levels, leading to vascular damage, elevated blood pressure, diabetes mellitus, and renal damage. Because genetic deletion of crucial parts of the renin-angiotensin system protect against obesity-related cardiovascular defects, we hypothesized that Dahl salt-sensitive (SS) rats, a model of chronically low plasma renin activity and angiotensin II levels, would be protected against vascular defects during diet-induced obesity compared with SS.13 BN consomic rats showing normal renin-angiotensin system regulation. We evaluated vascular function in middle cerebral arteries of SS or SS.13 BN rats fed high-fat (45% kcal from fat) versus normal-fat diet for 15 to 20 weeks from weaning. Endothelium-dependent relaxation in response to acetylcholine (10 −8 to 10 −4 mol/L) was restored in middle cerebral arteries of high-fat SS rats versus normal-fat diet controls, whereas vasodilation to acetylcholine was dramatically reduced in high-fat SS 13 BN rats versus normal-fat diet controls. These findings support the hypothesis that physiological levels of angiotensin II play an important role in maintaining normal vascular relaxation in cerebral arteries and suggest that the cerebral vasculature of the SS rat model is genetically protected against endothelial dysfunction in diet-induced obesity.
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Salt-sensitive rats fed a high-fat diet exhibit an improvement in endothelium-dependent vascular relaxation despite significant weight gain and the presence of cardiovascular risks including elevated blood pressure and reduced renal function.
“More striking is the finding that salt-sensitive (SS) rats fed high fat diet exhibit an improvement in endothelium-dependent vascular relaxation despite the significant weight gain and the presence of several cardiovascular risks including elevated blood pressure and reduced renal function (65).”
From Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis (2014) · cites this paper as [65]
The suppressed renin-angiotensin system appears to account for the improvement in endothelial function in obese salt-sensitive rats.
“The suppressed RAS appears to account for the improvement in endothelial function in obese SS rats (65).”
From Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis (2014) · cites this paper as [65]
Obesity is associated with several other changes in the kidney that promote the development of hypertension as well as chronic kidney disease and end-stage renal disease.
“Obesity is associated with several other changes in the kidney that promote the development of hypertension as well as chronic kidney disease and end-stage renal disease.”
From Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis (2014) · cites this paper as [65]
Vascular defects such as endothelial dysfunction are not universally associated with obesity.
“It should be noted, however, that vascular defects such as endothelial dysfunction are not universally associated with obesity. This is based on a number of studies showing the development of obesity without concomitant presence of vascular abnormalities (65;72).”
From Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis (2014) · cites this paper as [65]
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- Authors
- Beyer, A. M., Raffai, G., Weinberg, B., Fredrich, K., & Lombard, J. H.
- Affiliations
- Medical College of Wisconsin (US)
- From the Department of Physiology, Medical College of Wisconsin, Milwaukee, WI.
- Venue
- Hypertension
- Published
- 2012-08
- Volume
- 60
- Issue
- 2
- Pages
- 404-410
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- PMC
- PMC3444144
- OpenAlex
- W2106163955
- Cited by
- 31
- References
- 52
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 1 · 2016: 2 · 2015: 4 · 2014: 4 · 2013: 1 · 2012: 2
- FWCI
- 2.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R56HL065289, HL-65289, R01HL065289, HL 72920, R01HL092026, HL-92026, R01HL072920)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- Dahl salt-sensitive rats, diet-induced obesity, high-fat diet, renin-angiotensin system, angiotensin II, endothelium-dependent relaxation, middle cerebral artery, endothelial dysfunction, acetylcholine, vascular function, consomic rats
- MeSH terms
- Acetylcholine, Angiotensin II, Animals, Body Weight, Disease Models, Animal, Eating, Endothelium, Vascular, Male, Obesity, Renin, Renin-Angiotensin System, Vasodilation, Vasodilator Agents, Rats, Inbred Dahl, Middle Cerebral Artery, Rats, Diet, High-Fat
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