Increased coronary perfusion augments cardiac contractility in the rat through stretch-activated ion channels.
The role of stretch-activated ion channels (SACs) in coronary perfusion-induced increase in cardiac contractility was investigated in isolated isometrically contracting perfused papillary muscles from Wistar rats. A brief increase in perfusion pressure (3-4 s, perfusion pulse, n = 7), 10 repetitive perfusion pulses (n = 4), or a sustained increase in perfusion pressure (150-200 s, perfusion step, n = 7) increase developed force by 2.7 +/- 1.1, 7.7 +/- 2.2, and 8.3 +/- 2.5 mN/mm(2) (means +/- SE, P < 0.05), respectively. The increase in developed force after a perfusion pulse is transient, whereas developed force during a perfusion step remains increased by 5.1 +/- 2.5 mN/mm(2) (P < 0.05) in the steady state. Inhibition of SACs by addition of gadolinium (10 micromol/l) or streptomycin (40 and 100 micromol/l) blunts the perfusion-induced increase in developed force. Incubation with 100 micromol/l N(omega)-nitro-L-arginine [nitric oxide (NO) synthase inhibition], 10 micromol/l sodium nitroprusside (NO donation) and 0.1 micromol/l verapamil (L-type Ca(2+) channel blockade) are without effect on the perfusion-induced increase of developed force. We conclude that brief, repetitive, or sustained increases in coronary perfusion augment cardiac contractility through activation of stretch-activated ion channels, whereas endothelial NO release and L-type Ca(2+) channels are not involved.
Lamberts
R R
RR
Institute for Cardiovascular Research, Laboratory for Physiology, 1081 BT Amsterdam, The Netherlands. lamberts@physiol.med.vu.nl
van Rijen
M H P
MH
Sipkema
P
P
Fransen
P
P
Sys
S U
SU
Westerhof
N
N
D000818:Animals; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D007473:Ion Channels / Q000502:physiology*; D008297:Male; D008465:Mechanoreceptors / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010477:Perfusion; D011312:Pressure; D011674:Pulse; D051381:Rats; D017208:Rats, Wistar; D013307:Streptomycin / Q000494:pharmacology; D013997:Time Factors
D007473:Ion Channels; D009599:Nitroprusside; D019335:Nitroarginine; D013307:Streptomycin