Positive effect of bumetanide on contractile activity of ventricular cardiomyocytes.
Although the beneficial effects of loop-diuretics in relieving congestive heart failure and essential hypertension are well established, there has been limited investigation into the direct cardiac effect of these drugs. The aim of the present study was to investigate mechanical and electrophysiological effects of three loop-diuretics, namely, frusemide, bumetanide and torasemide, in ventricular cardiomyocytes isolated from rabbit myocardium. Contractile performance was assessed using a video edge detection method and effects on L-type Ca(2+) currents were determined using a 'perforated' patch-clamp technique. Unlike frusemide and torasemide, bumetanide produced concentration-dependent (3x10(-8) to 10(-5) M) increases in cell shortening and velocity of cell shortening. Neither frusemide, bumetanide nor torasemide exerted any action on peak Ca(2+) current amplitudes. In summary, the present investigation provides evidence for a direct contractile effect of the loop diuretic, bumetanide, in contrast to absence of effects by frusemide and torasemide, in ventricular cardiomyocytes isolated from rabbit myocardium.
Department of Therapeutics and Pharmacology, The Queen's University of Belfast, Whitla Medical Building, 97 Lisburn Road, BT9 7BL, Northern Ireland, Belfast, UK. e.kelso@qub.ac.uk
E
E
Kelso
B
B
McDermott
B
B
Silke
P
P
Spiers
D000818:Animals; D002034:Bumetanide / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004232:Diuretics / Q000494:pharmacology*; D005665:Furosemide / Q000494:pharmacology; D006352:Heart Ventricles / Q000166:cytology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D011817:Rabbits; D013449:Sulfonamides / Q000494:pharmacology; D000077786:Torsemide
D020746:Calcium Channels, L-Type; D002316:Cardiotonic Agents; D004232:Diuretics; D013449:Sulfonamides; D002034:Bumetanide; D005665:Furosemide; D007545:Isoproterenol; D000077786:Torsemide