Abstract
Differential effects of low-dose sacubitril and/or valsartan on renal disease in salt-sensitive hypertension. Am J Physiol Renal Physiol 319: F63-F75, 2020. First published May 28, 2020; doi:10.1152/ajprenal. 00125.2020.-Diuretics and renin-angiotensin system blockers are often insufficient to control the blood pressure (BP) in saltsensitive (SS) subjects. Abundant data support the proposal that the level of atrial natriuretic peptide may correlate with the pathogenesis of SS hypertension. We hypothesized here that increasing atrial natriuretic peptide levels with sacubitril, combined with renin-angiotensin system blockage by valsartan, can be beneficial for alleviation of renal damage in a model of SS hypertension, the Dahl SS rat. To induce a BP increase, rats were challenged with a high-salt 4% NaCl diet for 21 days, and chronic administration of vehicle or low-dose sacubitril and/or valsartan (75 μg/day each) was performed. Urine flow, Na+ excretion, and water consumption were increased on the high-salt diet compared with the starting point (0.4% NaCl) in all groups but remained similar among the groups at the end of the protocol. Upon salt challenge, we observed a mild decrease in systolic BP and urinary neutrophil gelatinase-associated lipocalin levels (indicative of alleviated tubular damage) in the valsartan-treated groups. Sacubitril, as well as sacubitril/valsartan, attenuated the glomerular filtration rate decline induced by salt. Alleviation of protein cast formation and lower renal medullary fibrosis were observed in the sacubitril/valsartan- A nd valsartan-treated groups, but not when sacubitril alone was administered. Interestingly, proteinuria was mildly mitigated only in rats that received sacubitril/valsartan. Further studies of the effects of sacubitril/valsartan in the setting of SS hypertension, perhaps involving a higher dose of the drug, are warranted to determine if it can interfere with the progression of the disease.
| Original language | English (US) |
|---|---|
| Pages (from-to) | F63-F75 |
| Journal | American Journal of Physiology - Renal Physiology |
| Volume | 319 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jul 2020 |
Bibliographical note
Funding Information:This work was supported by National Institutes of Health (NIH) Grant R00DK105160 (to D. V. Ilatovskaya), the Dialysis Clinic Inc Reserve Fund, the Medical University of South Carolina SCTR support program via NIH Grant UL1TR001450 (to D. V. Ilatovskaya), American Physiological Society (APS) Research Career Enhancement, and Lazaro J Mandel awards (to D. V. Ilatovskaya). In part, this work was supported by NIH Grant U54DA016511, Biomedical Laboratory Research and Development Service of the Veterans Office Office of Research and Development Award IK2BX003922, and the APS 2019 S&R Foundation Ryuji Ueno Award (all to K. Y. DeLeon-Pennell) as well as Cell and Molecular Imaging Shared Resource, Hollings Cancer Center, Medical University of South Carolina Grant P30CA138313 (to M. B. Gooz).
Publisher Copyright:
© 2020 the American Physiological Society.
Keywords
- Atrial natriuretic peptide
- Sacubitril
- Salt-sensitive hypertension
- Valsartan
- Angiotensin Receptor Antagonists/administration & dosage
- Aminobutyrates/administration & dosage
- Valsartan/administration & dosage
- Rats
- Male
- Sodium Chloride, Dietary
- Kidney Diseases/drug therapy
- Tetrazoles/administration & dosage
- Animals
- Blood Pressure/drug effects
- Rats, Inbred Dahl
- Drug Combinations
- Hypertension/drug therapy
PubMed: MeSH publication types
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, Non-P.H.S.
- Journal Article
- Research Support, N.I.H., Extramural