High‐salt diet promotes crystal deposition through hypertension in Dahl salt‐sensitive rat model

Abstract

Abbreviations & Acronyms 8-OHdG = 8-hydroxy-2 0deoxyguanosine Alox15b = arachidonate 15lipoxygenase AP = activity product BP = blood pressure BUN = blood urea nitrogen CaOx = calcium oxalate Cldn10 = claudin 10 Cp = ceruloplasmin Cr = creatinine DSs = Dahl salt-sensitive EA = ethylene glycol + alfacalcidol EG = ethylene glycol EPL = eplerenone HE = HS + EA HEE = HS + EA + EPL HR = heart rate HS = high salt IPA = ingenuity pathway analysis LOX = lipoxygenase MAPK = mitogen-activated protein kinase MMP7 = matrix metallopeptidase-7 MR = mineralocorticoid receptor NADPH = nicotinamide adenine dinucleotide phosphate RAS = renin-angiotensinaldosterone system ROS = reactive oxygen species TGF = transforming growth factor Umod = uromodulin Correspondence: KatsuhitoObjectives: To study the promotive effect of salt-induced hypertension on crystal deposition and urolithiasis using a salt-sensitive rat hypertension model. Methods: Hyperoxaluria and hypercalciuria were induced in male Dahl salt-sensitive rats with administration of ethylene glycol and alfacalcidol. Hypertension was induced by a high-salt diet. Eplerenone, a selective mineralocorticoid receptor antagonist, was given. Blood and urine were collected to evaluate renal function, electrolytes and the blood renin-angiotensin-aldosterone system. Renal calcium content was also evaluated. Histological examination, transcriptome analysis with DNA microarray and semiquantitative reverse transcriptase polymerase chain reaction were carried out. Results: A high-salt diet increased crystal deposition in Dahl salt-sensitive rats with hypertension, and eplerenone administration significantly suppressed it. The mRNA expression profile was associated with crystal formation, growth, adhesion and cellular injury, and it was regulated in the group exposed to a high-salt diet and ethylene glycol. Conclusions: A high-salt diet has a promotive effect on salt-sensitive hypertension and urolithiasis. This promotive effect can be prevented by eplerenone administration. Hence, salt-sensitive hypertension has promotive effects on crystal deposition in Dahl salt-sensitive rats.

Rodent models of hypertension

“…For Dahl SS rats, a high salt diet (HSD) consists of 2% to 4% NaCl, while the normal salt diets contain 0.3% to 0.5% NaCl. The dietary interventions range from 2 to 8 weeks (Bier et al, 2018; Mattson et al, 2005; Nakazawa et al, 2019).…”

Kidney Stone Prevention

“…High dietary sodium ingestion is accompanied by increased urinary calcium excretion [ 78 , 79 ] and CaOx crystal deposition in the kidney [ 80 , 81 ]. In pediatric patients, higher dietary sodium intake is also associated with calcium urolithiasis [ 82 ].…”

Evaluation of the Usefulness of Human Adipose-Derived Stem Cell Spheroids Formed Using SphereRing® and the Lethal Damage Sensitivity to Synovial Fluid In Vitro

“…Up-or downregulated genes were extracted using the GeneSpring GX software 14.9 (Agilent). IPA (Qiagen, Hilden, Germany) was used for gene network evaluation [45,46].…”