PDE1 or PDE5 inhibition augments NO‐dependent hypoxic constriction of porcine coronary artery via elevating inosine 3′,5′‐cyclic monophosphate level

Abstract

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Effect of phosphodiesterase‐4 inhibitor rolipram on colonic hypermotility in water avoidance stress rat model

“… 47 PDE1 or PDE5 inhibition could enhance the NO‐dependent hypoxic vasoconstriction of coronary artery. 48 Upregulation of PDE5 expression failed to reverse the depletion of neuronal NO and to impaired nNOS activity under sustained high blood pressure. 49 However, researchers have not yet determined whether NO is involved in rolipram‐induced colonic relaxation in an IBS model.…”

“…For instance, in a randomized controlled trial, sildenafil treatment improved vascular endothelial function in patients with cystic fibrosis by increasing NOS3 phosphorylation 47 . PDE1 or PDE5 inhibition could enhance the NO‐dependent hypoxic vasoconstriction of coronary artery 48 . Upregulation of PDE5 expression failed to reverse the depletion of neuronal NO and to impaired nNOS activity under sustained high blood pressure 49 .…”

Data_Sheet_1.PDF

“…• Cyanobacteria (Cadoret et al, 2005) • α-proteobacteria (Marden et al, 2011) • γ-proteobacteria (An et al, 2013) • UV-stress adaption (Cadoret et al, 2005) • Cyst formation (Marden et al, 2011) • Biofilm and virulence (An et al, 2013) 3 ,5 -cCMP 3 ,5 -cUMP Using modern mass spectrometry detected in various mammalian cell lines and different organs (Burhenne et al, 2011;Bähre et al, 2015). Additionally also found in zebrafish (Dittmar et al, 2015) and cUMP in a plant (Hartwig et al, 2014) • In general functions are currently mostly unknown (Seifert, 2017) • Both can activate some cAMP/cGMP effectors in vitro (Wolter et al, 2011;Zong et al, 2012) • cCMP potentially involved in processes such as tissue development and cell proliferation, immune responses modulation and platelet aggregation (Bloch et al, 1974;Anderson, 1982;Desch et al, 2010) • Specific cytidylate and uridylate cyclases just recently discovered in species of various phyla (Tal et al, 2021) • Synthesis stimulated by phage infection; activate downstream defense mechanisms (Tal et al, 2021) • Bacterial toxins [e.g., ExoY from P. aeruginosa (Beckert et al, 2014), CyaA from Bordetella pertussis (Göttle et al, 2010), edema factor from Bacillus anthracis (Göttle et al, 2010)] have been demonstrated to be capable of forming cCMP and cUMP 3 ,5 -cIMP Identified in isolated porcine coronary arteries (Chen et al, 2014) • In general functions are currently mostly unknown (Leung et al, 2015) • Involved in hypoxia−induced constriction of porcine coronary arteries (Chen et al, 2014;Nan et al, 2020) • Only very few data available • Detected in Corynebacterium murisepticum (Newton et al, 1998); specificity of the used method is however questioned (Seifert, 2015) 3 ,5 -cTMP 3 ,5 -cXMP Not yet detected in any biological samples using modern and sensitive mass spectrometry techniques…”