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Therapeutic Implications
Published in Thomas F. Lüscher, Paul M. Vanhoutte, The Endothelium: Modulator of Cardiovascular Function, 2020
Thomas F. Lüscher, Paul M. Vanhoutte
Nitrovasodilators have been used for the treatment of coronary artery disease or congestive heart failure for more than a century.6,121,952 The discovery that the main EDRF can be regarded as an endogenous nitrate has stimulated further research on the use and mechanism of action of nitrovasodilators (Figure 15).
Hypertensive Emergencies and Urgencies
Published in Giuseppe Mancia, Guido Grassi, Konstantinos P. Tsioufis, Anna F. Dominiczak, Enrico Agabiti Rosei, Manual of Hypertension of the European Society of Hypertension, 2019
Maria Lorenza Muiesan, Anna Paini, Claudia Agabiti Rosei, Fabio Bertacchini, Massimo Salvetti
Nitroglycerin, a venodilator, acts as an arteriolar dilator only in high doses. Intravenous administration of nitrovasodilators in the treatment of H-AHF in ED and ED-like settings is associated with an improvement in short-term symptoms, relatively few side effects and no impact on mortality (45).
Cell Biology
Published in John D Firth, Professor Ian Gilmore, MRCP Part 1 Self-Assessment, 2017
John D Firth, Professor Ian Gilmore
Nitric oxide lacks a classical receptor and has a unique mechanism of action. It diffuses freely into cells where it activates a soluble cytosolic form of guanylate cyclase, causing an elevation in cGMP. Nitrovasodilator drugs in clinical use, e.g. GTN, act as exogenous sources of nitric oxide, producing relaxation of blood vessels via increases in intracellular cGMP in vascular smooth muscle cells.
Vericiguat for the treatment of heart failure: mechanism of action and pharmacological properties compared with other emerging therapeutic options
Published in Expert Opinion on Pharmacotherapy, 2021
Jean-Sébastien Hulot, Jean-Noël Trochu, Erwan Donal, Michel Galinier, Damien Logeart, Pascal De Groote, Yves Juillière
Vericiguat is an oral drug with a once-daily dosing schedule that acts as a direct stimulator of the sGC enzyme. Vericiguat was developed to be indicated upon regulatory approval as a first-in-class therapy for WCHF [20]. Vericiguat has an optimized pharmacokinetic profile with a higher half-life as compared with the first sGC stimulator, riociguat, thus allowing the development of a once-daily oral administration regimen [21]. Vericiguat works in synergy with endogenous NO [13,22] which is considered as a nitrovasodilator to produce cGMP under low-NO conditions. Accordingly, vericiguat treatment is expected to restore the impaired NO–sGC–cGMP pathway leading to a diversity of pharmacological effects including improvements in cardiac and vascular functions, and reduction in pro-fibrotic and inflammatory pathways [11,20] (Figure 1). By increasing cGMP, vericiguat is also estimated to induce vasorelaxation and improve regulation of vascular tone and myocardial dysfunction [13,23,24,25]. It would also attenuate left-ventricular remodeling by inducing PKG-mediated phosphorylation of titin following the activation of PKG by cGMP [25]. On the hemodynamic level and based on the CHEST and PATENT studies on riociguat [26,27], vericiguat is believed to improve the cardiac index through its vasodilator effect without exhaustion of this effect in contrast with other vasodilators. As for the extra-cardiac effects of vericiguat, this molecule has antiagregant and antifibrotic (potential benefit in kidney failure) properties [28]. Thus, vericiguat is anticipated to improve myocardial and endothelial functions in patients with HF and potentially with WCHF [9].
Metal Nanoparticles in Infection and Immunity
Published in Immunological Investigations, 2020
Endothelial NOS, or eNOS, generates NO to regulate vascular tone, and neuronal NOS, or nNOS, generates NO which acts as a neurotransmitter (Furchgott 1996). The inducible form, called iNOS, is most important in antimicrobial immunity, and once fully induced, produces the largest amounts of NO (Murad 2006). Many commonly used drugs, called nitrovasodilators, act via release of nitric oxide, including nitroglycerin, nitroprusside, and isosorbide mononitrate.