Figure 1 NOS–NO signalling in cardiovascular tissues Figure 1 | NOS–NO signalling in cardiovascular tissues. In the vessel wall, nitric oxide (NO) synthesis by endothelial nitric oxide synthase (eNOS) in endothelial cells regulates vascular smooth muscle cell (VSMC) relaxation, mediates angiogenesis, inhibits VSMC proliferation, and through its diffusion to the vessel lumen inhibits platelet aggregation and thrombosis. S-nitrosylation of haemoglobin and/or reduction of nitrites (NO2−) by deoxyhaemoglobin promotes NO release and subsequent NO-mediated relaxation in hypoxic tissues. Diffusion and bioavailability of NO in VSMCs are regulated by haemoglobin-α (Hb-α) at the myoendothelial junction and by cytoglobin (CYGB) in muscle cells. Synthesis of NO by neuronal nitric oxide synthase (nNOS) within VSMCs also contributes to regulate vascular tone. In cardiac myocytes, autocrine and paracrine effects of NO from eNOS and nNOS modulate cardiac contractility through regulation of excitation–contraction coupling (including in response to stretch and β1-adrenergic stimulation), relaxation, and mitochondrial respiration. nNOS expression in cardiac nerves and postsynaptic eNOS modulate the ortho–parasympathetic balance towards reinforced parasympathetic (vagal) transmission leading to reduced heart rate. β1, adrenergic receptor β1; ACh, acetylcholine; m2, muscarinic acetylcholine receptor m2; NA, noradrenaline; SNO, S-nitrosothiol; SR, sarcoplasmic reticulum; T-tubule, transverse-tubule. Farah, C. et al. (2018) Nitric oxide signalling in cardiovascular health and disease Nat. Rev. Cardiol. doi:10.1038/nrcardio.2017.224