Nitric oxide is an important signalling molecule in the cardiovascular system. Here we tested whether and how NO regulates right atrial functions in biopsies from patients in sinus rhythm (SR).
Methods.
Experiments were performed on right atrial biopsies from 65 patients in SR. Activation of the L-type calcium channels with successive release of Ca2+ from the sarcoplasimic reticulum stores induces cardiomyocyte contraction. Therefore, measurement of calcium current (ICa,L) in isolated cardiomyocytes and force of contraction (Fc) of trabeculae were used as read-out for the nitric oxide signaling pathway. S-nitroso-N-acetylpenicillamine was used as NO donor (SNAP).
Results
In cardiomyocytes from SR patients SNAP (100 µM) increased basal ICa,L from 6.05 ± 0.28 pA/pF to 9.11± 0.43 pA/pF (p < 0.001, n/N =127/65). In multicellular trabeculae SNAP had a small positive inotropic effect at 300 µM and 1 mM. SNAP effects are mediated via soluble guanylate cyclase (sGC), phosphodiesterase 3 (PDE3), and PKA. SNAP, as well as, the PDE3 inhibitor, cilostamide, stimulated basal ICa,L. However, SNAP reduced cilostamide-stimulated ICa,L through activation of PDE2.
Conclusion
NO exerts dual effects on ICa,L: increase of basal current and inhibition of cAMP-stimulated current.
Notes to editor
Authors: N. Rozmaritsa, T. Christ, C. Poulet, E. Wettwer, U. Ravens
The content of this article reflects the personal opinion of the
author/s and is not necessarily the official position of the
European Society of Cardiology.