Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Generation of nitric oxide (NO) by the nitric oxide synthase (NOS) enzymes plays multiple signalling roles in every organ system, with crucial roles in the cardiovascular system, mediated by endothelial nitric oxide synthase (eNOS, encoded by NOS3) and neuronal nitric oxide synthase (nNOS, encoded by NOS1) in regulation of blood pressure, flow, oxygen delivery and cardiac function. Loss of normal NO-mediated functions in cardiovascular disease state is associated with changes in nitroso-redox signalling that are not dependent solely upon altered NO generation, but increased generation of reactive oxygen species (ROS). The NOS enzymes can also generate ROS, in a catalytic mode whereby the generation of NO from L-arginine is 'uncoupled' from the reduction of molecular oxygen. NOS uncoupling is determined by several factors, including the availability and oxidation state of the required NOS cofactor, tetrahydrobiopterin (BH4). The duality of NOS functions as enzymes that generate both NO and ROS under different regulatory states has emerged as an important pathophysiologic mechanism, and is a potential therapeutic target, via agents that can maintain or restore NOS coupling, for example via effects on BH4 availability.

Original publication

DOI

10.1007/164_2020_390

Type

Journal article

Journal

Handb Exp Pharmacol

Publication Date

2021

Volume

264

Pages

339 - 352

Keywords

Cardiovascular disease, Endothelium, Nitric oxide, Reactive oxygen species, Tetrahydrobiopterin, Biopterin, Humans, Nitric Oxide, Nitric Oxide Synthase, Nitric Oxide Synthase Type III, Reactive Oxygen Species