The effect of atrial natriuretic factor on force development in rat cardiac trabeculae.
Studies in single cardiac muscle cells have demonstrated that atrial natriuretic factor decreases the L-type calcium current. Recent investigations in human atrial cells have also demonstrated that atrial natriuretic factor causes a voltage-dependent reduction in sodium channel activity and thus may reduce intracellular calcium via decreased activity of the sodium-calcium exchange mechanism. By reducing intracellular calcium, atrial natriuretic factor may have a negative inotropic effect on cardiac muscle. To characterize the effect of atrial natriuretic factor on the development of force, we studied the force-sarcomere length relationship in 11 right ventricular rat trabeculae, both before and after exposure of the muscles to increasing concentrations of atrial natriuretic factor. Sarcomere length was measured by laser diffraction techniques and controlled by a servomotor system. The addition of atrial natriuretic factor to the superfusion solution, at concentrations of 10(-9)-10(-7) M, increased stimulus threshold, reduced peak twitch force in a dose-dependent manner by 38% (maximum), and reduced time to peak twitch force by 15% (maximum). Incubation of muscle preparations with concentrations of atrial natriuretic factor below 10(-9) M had no effect on force generation. The negative inotropic effect of atrial natriuretic factor was associated with a change in the shape of the force-sarcomere length relationship, similar to a reduction of the extracellular calcium concentration. ANF (10(-7) M) had no effect on the rate of decay of force following post extra-systolic potentiation. These observations are consistent with the assumption that the negative inotropic effect of atrial natriuretic factor is mediated by reduction of calcium entry into the cardiac cell.
Stone
J A
JA
Department of Medicine, University of Calgary, Alta., Canada.
Backx
P H
PH
ter Keurs
H E
HE
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D003864:Depression, Chemical; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D012964:Sodium / Q000502:physiology; D013599:Systole / Q000502:physiology
C472610:atrial natriuretic peptide, rat; D009320:Atrial Natriuretic Factor; D012964:Sodium; D002118:Calcium