Endothelin-A Receptor Antagonism Attenuates the Hypertension and Renal Injury in Dahl Salt-Sensitive Rats
Abstract
The aim of this study was to examine the role of endothelin-A (ET A) receptors in mediating the hypertension and renal injury associated with high salt intake in Dahl salt-sensitive (DS) rats. To achieve this goal, we examined the effects of chronic selective ET A antagonist (A-127722) treatment at a dose of 10 mg/kg/d on arterial pressure, renal function, and morphology in DS and Dahl salt-resistant (DR) rats placed on a high sodium (8% NaCl) diet (HSD) for 3 weeks. Placement of DS rats (n=13) on HSD for 3 weeks caused a progressive increase in systolic pressure (from 118±3 to 186±15 mm Hg). The increase in systolic pressure was significantly attenuated (from 125±4 to 167±12 mm Hg) in DS rats treated with A-127722 (n=13). Mean arterial pressure (MAP) measured directly at the end of the study was also significantly lower by 18 mm Hg (P<.02) in the DS rats treated with A-127722. The slope of the chronic pressure-natriuresis curve was shifted to the right in DS rats and to the left by chronic ET A receptor blockade in DS rats. The hypertension in DS rats was associated with marked proteinuria (from 4.1±1.1 to 74.3±5.3 mg/24 h/100 g body weight) that was significantly attenuated (from 5.7±1.2 to 55.2±6.5 mg/24 h/100 g body weight) in DS rats treated with A-127722. The percentage of glomeruli displaying fibrosis, hypercellularity, and hyalinization was also significantly reduced after treatment with A-127722 in DS rats. Arterial pressure, protein excretion, renal hemodynamics, and morphologic structure were not significantly changed in response to ET A receptor blockade in DR rats placed on HSD. These data indicate that endothelin-A receptor activation may play a role in the exacerbation of hypertension and development of renal injury in DS rats.
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Self-citation
- Authors
- Kassab, S., Miller, M. T., Novak, J., Reckelhoff, J., Clower, B., & Granger, J. P.
- Affiliations
- University of Mississippi Medical Center (US)
- Venue
- Hypertension
- Published
- 1998-01
- Volume
- 31
- Issue
- 1
- Pages
- 397-402
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2141528467
- Cited by
- 110
- References
- 40
- Citations by year
- 2025: 1 · 2024: 2 · 2022: 1 · 2020: 3 · 2019: 2 · 2018: 7 · 2017: 1 · 2016: 2 · 2015: 6 · 2014: 4 · 2013: 2 · 2012: 5
- FWCI
- 5.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (HL-51971)
- National Heart, Lung, and Blood Institute (HL-38499, HL‐51971, P01HL051971)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Keywords
- endothelin-A receptor antagonism, Dahl salt-sensitive rats, Dahl salt-resistant rats, salt-sensitive hypertension, high-salt diet, kidney injury, proteinuria, pressure natriuresis, glomerular fibrosis, renal hemodynamics, endothelin-1
- MeSH terms
- Atrasentan, Animals, Blood Pressure, Diet, Sodium-Restricted, Glomerular Filtration Rate, Hemodynamics, Hypertension, Kidney, Male, Natriuresis, Potassium, Proteinuria, Pyrrolidines, Rats, Inbred Strains, Regional Blood Flow, Sodium, Sodium, Dietary, Systole, Receptor, Endothelin A, Rats, Endothelin Receptor Antagonists
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