Differential effects of low-dose sacubitril and/or valsartan on renal disease in salt-sensitive hypertension
| Autor: | Kristine Y. DeLeon-Pennell, Miguel Troncoso, Mark Domondon, Yuliia Kashyrina, Iuliia Polina, Wayne R. Fitzgibbon, Rebecca Fox, Ryan Schibalski, Daria V. Ilatovskaya, Valeriia Y. Vasileva, Monika Gooz, Anastasia V. Sudarikova |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Physiology Urinary system Tetrazoles Renal function Blood Pressure 030204 cardiovascular system & hematology Sacubitril Excretion Angiotensin Receptor Antagonists 03 medical and health sciences 0302 clinical medicine Atrial natriuretic peptide Internal medicine Animals Medicine Sodium Chloride Dietary Rats Inbred Dahl Proteinuria business.industry Aminobutyrates Biphenyl Compounds Rats Drug Combinations 030104 developmental biology Blood pressure Endocrinology Valsartan Hypertension Kidney Diseases medicine.symptom business Research Article medicine.drug |
| Zdroj: | Am J Physiol Renal Physiol |
| ISSN: | 1522-1466 1931-857X |
| DOI: | 10.1152/ajprenal.00125.2020 |
| Popis: | Diuretics and renin-angiotensin system blockers are often insufficient to control the blood pressure (BP) in salt-sensitive (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- and 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. |
| Databáze: | OpenAIRE |
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