Candesartan (1 mg/kg/day) significantly reversed the increased abundance and apical targeting of AQP2 and p-AQP2, as well as increased NHE3 and NKCC2 expression, in rats with induced heart failure.
Does candesartan reverse changes in renal sodium and water transporters in rats with experimentally induced heart failure?
Angiotensin II AT1 receptor blockade with candesartan reverses the upregulation of key renal water and sodium transporters in experimental heart failure, highlighting the role of angiotensin II in HF-associated fluid retention.
Heart failure (HF) was induced by ligation of the left anterior descending artery (LAD). Left ventricular end-diastolic pressure (LVEDP) >25 mmHg (at day 23 after LAD ligation) was the inclusion criterion. The rats were divided into three groups: sham-operated (Sham, n = 23, LVEDP: 5.6 +/- 0.6 mmHg), HF (n = 14, LVEDP: 29.4 +/- 1.4 mmHg), and candesartan (1 mg.kg(-1).day(-1) sc)-treated HF (HF + Can, n = 9, LVEDP: 29.2 +/- 1.2 mmHg). After 7 days (i.e., 29 days after LAD ligation) semiquantitative immunoblotting revealed increased abundance of inner medulla aquaporin-2 (AQP2) and AQP2 phosphorylated at Ser(256) (p-AQP2) in HF. There was also markedly enhanced apical targeting of AQP2 and p-AQP2 in inner medullary collecting duct (IMCD) in HF compared with Sham rats, shown by immunocytochemistry. Candesartan treatment significantly reversed the increases in both AQP2 and p-AQP2 expression and targeting. In contrast, there were only modest changes in other collecting duct segments. Semiquantitative immunoblots revealed increased expression of type 3 Na(+)/H(+) exchanger (NHE3) and Na(+)-K(+)-2Cl(-) cotransporter (NKCC2) in kidneys from HF compared with Sham rats: both effects were reversed or prevented by candesartan treatment. The protein abundance of alpha-epithelial sodium channel (alpha-ENaC) was increased while beta-ENaC and gamma-ENaC expression was decreased in the cortex and outer stripe of the outer medulla in HF compared with Sham rats, which was partially reversed by candesartan treatment. These findings strongly support an important role of angiotensin II in the pathophysiology of renal water and sodium retention associated with HF.
Lütken et al. (Thu,) conducted a other in Heart failure (n=46). Candesartan vs. Sham-operated and untreated HF was evaluated on Changes in renal AQP2, ENaC, and NHE3 expression and targeting. Candesartan (1 mg/kg/day) significantly reversed the increased abundance and apical targeting of AQP2 and p-AQP2, as well as increased NHE3 and NKCC2 expression, in rats with induced heart failure.