TY - JOUR
T1 - Differential effects of low-dose sacubitril and/or valsartan on renal disease in salt-sensitive hypertension
AU - Polina, Iuliia
AU - Domondon, Mark
AU - Fox, Rebecca
AU - Sudarikova, Anastasia V.
AU - Troncoso, Miguel
AU - Vasileva, Valeriia Y.
AU - Kashyrina, Yuliia
AU - Gooz, Monika Beck
AU - Schibalski, Ryan S.
AU - DeLeon-Pennell, Kristine Y.
AU - Fitzgibbon, Wayne R.
AU - Ilatovskaya, Daria V.
N1 - Publisher Copyright:
© 2020 the American Physiological Society.
PY - 2020/7
Y1 - 2020/7
N2 - 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.
AB - 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.
KW - Atrial natriuretic peptide
KW - Sacubitril
KW - Salt-sensitive hypertension
KW - Valsartan
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U2 - 10.1152/ajprenal.00125.2020
DO - 10.1152/ajprenal.00125.2020
M3 - Article
C2 - 32463726
AN - SCOPUS:85087110712
SN - 1931-857X
VL - 319
SP - F63-F75
JO - American Journal of Physiology - Renal Physiology
JF - American Journal of Physiology - Renal Physiology
IS - 1
ER -