Changes of renal AQP2, ENaC, and NHE3 in experimentally induced heart failure: response to angiotensin II AT1 receptor blockade.

Abstract

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.

• Authors: Sophie C Lütken, Soo Wan Kim, Thomas Jonassen, David Marples, Mark A Knepper, Tae-Hwan Kwon, Jørgen Frøkiaer, Søren Nielsen
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 297 Issue 6 Pg. F1678-88 (Dec 2009) ISSN: 1522-1466 [Electronic] United States
• PMID: 19776175 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Aquaporin 2
• Benzimidazoles
• Biphenyl Compounds
• Epithelial Sodium Channels
• Slc12a1 protein, rat
• Slc9a3 protein, rat
• Sodium-Hydrogen Exchanger 3
• Sodium-Hydrogen Exchangers
• Sodium-Potassium-Chloride Symporters
• Solute Carrier Family 12, Member 1
• Tetrazoles
• Angiotensin II
• Sodium
• 11-beta-Hydroxysteroid Dehydrogenase Type 2
• Potassium
• candesartan

Topics

• 11-beta-Hydroxysteroid Dehydrogenase Type 2 (metabolism)
• Angiotensin II (metabolism)
• Angiotensin II Type 1 Receptor Blockers (pharmacology)
• Animals
• Aquaporin 2 (metabolism)
• Benzimidazoles (pharmacology)
• Biphenyl Compounds
• Body Water (metabolism)
• Epithelial Sodium Channels (metabolism)
• Heart Failure (metabolism)
• Kidney (drug effects, metabolism)
• Kidney Cortex (metabolism)
• Kidney Medulla (metabolism)
• Phosphorylation
• Potassium (urine)
• Rats
• Rats, Wistar
• Sodium (metabolism, urine)
• Sodium-Hydrogen Exchanger 3
• Sodium-Hydrogen Exchangers (metabolism)
• Sodium-Potassium-Chloride Symporters (metabolism)
• Solute Carrier Family 12, Member 1
• Tetrazoles (pharmacology)
• Tissue Distribution