Nitric oxide signalling in cardiovascular health and disease, 2018, Farah et al

Nitric oxide signalling in cardiovascular health and disease
Charlotte Farah, Lauriane Y. M. Michel, Jean-Luc Balligand

Abstract
Nitric oxide (NO) signalling has pleiotropic roles in biology and a crucial function in cardiovascular homeostasis. Tremendous knowledge has been accumulated on the mechanisms of the nitric oxide synthase (NOS)–NO pathway, but how this highly reactive, free radical gas signals to specific targets for precise regulation of cardiovascular function remains the focus of much intense research.

In this Review, we summarize the updated paradigms on NOS regulation, NO interaction with reactive oxidant species in specific subcellular compartments, and downstream effects of NO in target cardiovascular tissues, while emphasizing the latest developments of molecular tools and biomarkers to modulate and monitor NO production and bioavailability.

Key Points

• The three isoforms of nitric oxide synthase subserve distinct, but coordinated, functions through their subcellular confinement in cardiac and vascular cells
• The redox environment dictates the fate of nitric oxide and pathophysiological effects
• Multiple regulatory points of downstream effectors ensure signalling specificity and allow therapeutic modulation
• New techniques for monitoring nitric oxide bioavailability will allow efficient tailoring of treatment

PubMed | Link (paywalled)

 

Given recent findings of alterations in NO production/function in endothelial cells and glial cells in ME/CFS, this is likely to be a useful review paper. Despite being paywalled, hopefully it's OK to post the figures to allow for discussion. As you can imagine from the figures, the paper itself is quite dense.


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.

 

Figure 3
NOS–NO pathway in vascular beds in health and disease.

 

Cardiac nitric oxide scavenging: role of myoglobin and mitochondria

https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP284446