Increased expression and function of the myocardial Na-K-2Cl cotransporter in failing rat hearts.
Recent studies indicate a role of the Na-K-2Cl cotransporter (NKCC) in regulation of myocardial function. However, potential pathophysiological properties of NKCC in conditions like myocardial infarction (MI) and heart failure have not been explored. We investigated the cellular localization of myocardial NKCC and whether myocardial NKCC levels are changed upon induction of post-infarction heart failure in rats. Immunohistochemical analysis demonstrated extensive distribution of NKCC in normal rat myocardium with fairly strong expression in cardiomyocytes, fibroblasts, vascular endothelial cells, as well as smooth muscle cells. Myocardial mRNA levels of NKCC were investigated at 2, 7 and 28 days after induction of MI or sham operation, but no changes were found. Cardiomyocytes and non-cardiomyocytes were isolated 7 days after induction of MI or sham operation. An approximately 2-fold increase of the NKCC mRNA levels was found in isolated cardiomyocytes from heart failure rats compared to that of sham-operated rats (P < 0.001), whereas a trend towards decreased mRNA levels of NKCC in isolated non-cardiomyocytes was observed. In addition, we found a bumetanide sensitive (86)Rb(+) influx mechanism present in the hearts after induction of MI (P < 0.05). Thus, our data indicate cardiomyocyte specific increase in NKCC mRNA levels and increased NKCC activity in post-infarction heart failure. Our results may indicate a potential role of NKCC during post-infarction remodeling.
Andersen
Geir Oystein
GO
Department of Pharmacology, University of Oslo, Box 1057, Blindern, 0316 Oslo, Norway. g.o.andersen@labmed.uio.no
Oie
Erik
E
Vinge
Leif Erik
LE
Yndestad
Arne
A
Attramadal
Håvard
H
Skomedal
Tor
T
Osnes
Jan Bjørn
JB
D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D002303:Cardiac Output, Low / Q000209:etiology / Q000378:metabolism*; D005786:Gene Expression Regulation; D008297:Male; D009203:Myocardial Infarction / Q000150:complications; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012414:Rubidium Radioisotopes / Q000378:metabolism; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics / Q000378:metabolism*; D020257:Ventricular Remodeling
D012333:RNA, Messenger; D012414:Rubidium Radioisotopes; D049994:Sodium Potassium Chloride Symporter Inhibitors; D028021:Sodium-Potassium-Chloride Symporters; D002034:Bumetanide