Figure 3
From: Bench-to-bedside review: Nitric oxide in critical illness – update 2008
Bimodal actions of nitric oxide in cardiac myocytes. (a) At low concentrations, nitric oxide (NO) stimulates adenylate cyclase (AC) and acts through guanylate cyclase (GC) to inhibit phosphodiesterase (PDE), both of which increase cAMP levels, thus stimulating cAMP-dependent protein kinase A (PKA). PKA increases contractility by opening voltage-operated calcium channels (VOCs) on the plasma membrane and by stimulating ryanodine receptors (RyRs) on the sarcoplasmic reticulum (SR). (b) At high concentrations, however, NO produces much larger amounts of cyclic GMP (cGMP), which stimulates the cGMP-dependent protein kinase G (PKG). PKG decreases contractility by hyperpolarizing the plasma membrane, decreasing calcium influx through voltage-sensitive channels, and also by decreasing sensitivity of troponin T to calcium [19]. Reprinted from Life Sciences, 81(10), R. Rastaldo, P. Pagliaro, S. Cappello, C. Penna, D. Mancardi, N. Westerhof and G. Losano, Nitric oxide and cardiac function, 15 Pages, Copyright (2007), with permission from Elsevier.