Coronary perfusion and muscle lengthening increase cardiac contraction: different stretch-triggered mechanisms.
An increase in coronary perfusion, transversal stretch of the myocardium, increases developed force (F(dev)) (Gregg effect) through activation of stretch-activated ion channels (SACs). Lengthening of the muscle, longitudinal stretch of the myocardium, causes an immediate increase in F(dev) followed by a slow F(dev) increase (Anrep effect). In isometrically contracting perfused papillary muscles of Wistar rats, we investigated whether both effects were based on similar stretch-induced mechanisms by measuring F(dev) and intracellular Ca(2+) concentration ([Ca(2+)](i)) after a muscle length increase from 85% to 95% L(max) (length at which maximal isometric force develops) at low and high coronary perfusion before and after inhibition of SACs with gadolinium (10 micromol/l Gd(3+)). The increase of F(dev) and peak [Ca(2+)](i) by the Gregg effect was of similar magnitude as the Anrep effect (from 3.5 +/- 0.8 to 3.9 +/- 1.2 mN/mm(2) and from 3.0 +/- 0.7% to 3.8 +/- 0.9% normalized [Ca(2+)](i), means +/- SE). SAC blockade completely blunted the increase of F(dev) and peak [Ca(2+)](i) by the Gregg effect; however, it did not affect the Anrep effect. The slow force response, but not the calcium response, was augmented by an increase in coronary perfusion. Therefore, increased coronary perfusion, transversal stretch of the myocardium, and muscle lengthening, longitudinal stretch of the myocardium, increase myocardial contraction in the rat through different stretch-triggered mechanisms.
Lamberts
Regis R
RR
Laboratory for Physiology, Institute for Cardiovascular Research, Vrije Universiteit University Medical Center, Amsterdam 1081 BT, The Netherlands. lamberts@physiol.med.vu.nl
Van Rijen
Mattie H P
MH
Sipkema
Pieter
P
Fransen
Paul
P
Sys
Stanislas U
SU
Westerhof
Nico
N
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003326:Coronary Circulation / Q000502:physiology*; D005682:Gadolinium / Q000494:pharmacology; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000502:physiology*; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D010210:Papillary Muscles / Q000166:cytology / Q000502:physiology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013307:Streptomycin / Q000494:pharmacology
D011500:Protein Synthesis Inhibitors; D005682:Gadolinium; D002118:Calcium; D013307:Streptomycin