Endothelin A receptor blocker and calcimimetic in the adenine rat model of chronic renal insufficiency

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dc.contributor.author Törmänen, Suvi
dc.contributor.author Pörsti, Ilkka
dc.contributor.author Lakkisto, Päivi
dc.contributor.author Tikkanen, Ilkka
dc.contributor.author Niemelä, Onni
dc.contributor.author Paavonen, Timo
dc.contributor.author Mustonen, Jukka
dc.contributor.author Eräranta, Arttu
dc.date.accessioned 2017-10-29T13:01:25Z
dc.date.available 2017-10-29T13:01:25Z
dc.date.issued 2017-10-27
dc.identifier.citation BMC Nephrology. 2017 Oct 27;18(1):323
dc.identifier.uri http://hdl.handle.net/10138/228071
dc.description.abstract Abstract Background We studied whether endothelin receptor antagonist and calcimimetic treatments influence renal damage and kidney renin-angiotensin (RA) components in adenine-induced chronic renal insufficiency (CRI). Methods Male Wistar rats (n = 80) were divided into 5 groups for 12 weeks: control (n = 12), 0.3% adenine (Ade; n = 20), Ade + 50 mg/kg/day sitaxentan (n = 16), Ade + 20 mg/kg/day cinacalcet (n = 16), and Ade + sitaxentan + cinacalcet (n = 16). Blood pressure (BP) was measured using tail-cuff, kidney histology was examined, and RA components measured using RT-qPCR. Results Adenine caused tubulointerstitial damage with severe CRI, anemia, hyperphosphatemia, 1.8-fold increase in urinary calcium excretion, and 3.5-fold and 18-fold increases in plasma creatinine and PTH, respectively. Sitaxentan alleviated tubular atrophy, while sitaxentan + cinacalcet combination reduced interstitial inflammation, tubular dilatation and atrophy in adenine-rats. Adenine diet did not influence kidney angiotensin converting enzyme (ACE) and AT4 receptor mRNA, but reduced mRNA of renin, AT1a, AT2, (pro)renin receptor and Mas to 40–60%, and suppressed ACE2 to 6% of that in controls. Sitaxentan reduced BP by 8 mmHg, creatinine, urea, and phosphate concentrations by 16–24%, and PTH by 42%. Cinacalcet did not influence BP or creatinine, but reduced PTH by 84%, and increased hemoglobin by 28% in adenine-rats. The treatments further reduced renin mRNA by 40%, while combined treatment normalized plasma PTH, urinary calcium, and increased ACE2 mRNA 2.5-fold versus the Ade group (p < 0.001). Conclusions In adenine-induced interstitial nephritis, sitaxentan improved renal function and tubular atrophy. Sitaxentan and cinacalcet reduced kidney renin mRNA by 40%, while their combination alleviated tubulointerstitial damage and urinary calcium loss, and increased kidney tissue ACE2 mRNA.
dc.publisher BioMed Central
dc.subject Chronic kidney disease
dc.subject Sitaxentan
dc.subject Cinacalcet
dc.subject Creatinine
dc.subject Parathyroid hormone
dc.subject Renal renin-angiotensin system
dc.title Endothelin A receptor blocker and calcimimetic in the adenine rat model of chronic renal insufficiency
dc.date.updated 2017-10-29T13:01:25Z
dc.language.rfc3066 en
dc.rights.holder The Author(s).
dc.type.uri http://purl.org/eprint/entityType/ScholarlyWork
dc.type.uri http://purl.org/eprint/entityType/Expression
dc.type.uri http://purl.org/eprint/type/JournalArticle

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