Novel therapies for cyclic GMP control of vascular smooth muscle growth.

American Journal of Therapeutics
David A Tulis

Abstract

Cyclic GMP, guanosine 3',5'-cyclic monophosphate, is a critical and multifunctional second-messenger molecule that mediates diverse physiological and pathophysiological functions in cardiac and vascular tissues. Synthesized through nitric oxide, carbon monoxide, and/or natriuretic peptide-mediated guanylate cyclase stimulation and guanosine triphosphate dephosphorylation, cyclic GMP is capable of stimulating a cascade of serine/threonine kinase events, including signaling through cyclic GMP- and/or cyclic AMP-dependent protein kinases, eliciting protein kinase-independent actions such as modulation of ion channels or transporters, or undergoing hydrolytic degradation through actions of cyclic GMP-regulated phosphodiesterases. Substrates, enzymes, cofactors, and associated variables in this multifaceted system have historically been targets of vital pharmacotherapies with perhaps most common the use of vascular smooth muscle-targeting organonitrates in cardiac patients and phosphodiesterase inhibitors in individuals with erectile dysfunction. Accumulating basic science and clinical evidence, however, suggests that cyclic GMP signaling is compromised under conditions of disease or elevated physiological stresses. Moreover, nitric...Continue Reading

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Citations

Apr 4, 2009·Journal of Cardiovascular Pharmacology and Therapeutics·Amit N KeswaniDavid A Tulis
Mar 3, 2012·Toxicology and Applied Pharmacology·Tsong-Long HwangYao-Ching Fang
Dec 12, 2012·European Journal of Pharmacology·Kwok-Keung LamMao-Hsiung Yen
Jan 26, 2018·Journal of Cardiovascular Development and Disease·Nathan A HollandDavid A Tulis
Mar 25, 2016·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Qiuyu YaoHongfang Jin

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