Advertisement

 

 

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

Endothelin A receptor blocker and calcimimetic in the adenine rat model of chronic renal insufficiency.
Author Information (click to view)

Törmänen S, Pörsti I, Lakkisto P, Tikkanen I, Niemelä O, Paavonen T, Mustonen J, Eräranta A,


Törmänen S, Pörsti I, Lakkisto P, Tikkanen I, Niemelä O, Paavonen T, Mustonen J, Eräranta A, (click to view)

Törmänen S, Pörsti I, Lakkisto P, Tikkanen I, Niemelä O, Paavonen T, Mustonen J, Eräranta A,

Advertisement
Share on FacebookTweet about this on TwitterShare on LinkedIn

BMC nephrology 2017 10 2718(1) 323 doi 10.1186/s12882-017-0742-z
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.

Submit a Comment

Your email address will not be published. Required fields are marked *

6 − two =

[ HIDE/SHOW ]