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 mumol/l) or streptomycin (40 and 100 mumol/l) blunts the perfusion-induced increase in developed force. Incubation with 100 mumol/l N-omega-nitro-L-arginine [nitric oxide (NO) synthase inhibition], 10 mumol/l sodium nitroprusside (NO donation) and 0.1 mumol/l verapamil (L-type Ca2+ 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 Ca2+ channels are not involved.