Recent applications of phosphodiesterase (PDE5) inhibition assays for detecting adulterated sexual enhancement products

2021 ◽  
Author(s):  
Michael F. Santillo
Keyword(s):  
Pde5 Inhibition

scholarly journals The effect of PDE5 inhibition on the erectile function in streptozotocin-induced diabetic rats

2004 ◽  
Vol 17 (2) ◽  
pp. 134-141 ◽  
Author(s):  
G J Ahn ◽  
Y S Sohn ◽  
K K Kang ◽  
B O Ahn ◽  
J W Kwon ◽  
...  
Keyword(s):  
Erectile Function ◽  
Diabetic Rats ◽  
Pde5 Inhibition

Abstract 423: Proteasome Priming by Protein Kinase G Protects Against Myocardial Ischemia-reperfusion Injury

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Xuejun Wang ◽  
Erin J Terpstra ◽  
Eduardo Callegari ◽  
Chengjun Hu ◽  
Hanming Zhang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Myocardial Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Underlying Mechanism ◽  
26S Proteasome ◽  
Transgenic Mouse Line ◽  
Pde5 Inhibition ◽  
Myocardial Ischemia Reperfusion

Cardiac proteasome functional insufficiency is implicated in a large subset of heart disease and has been experimentally demonstrated to play an essential role in cardiac proteotoxicity, including desmin-related cardiomyopathy and myocardial ischemia-reperfusion (I-R) injury. Pharmacological inhibition of phosphodiesterase 5 (PDE5) via sildenafil for example, which can stabilize cGMP and thereby increase cGMP-dependent protein kinase (PKG) activity, is consistently reported to protect against I-R injury; however, the underlying mechanism is not fully understood. We have recently discovered that PKG activation enhances proteasomal degradation of misfolded proteins (Ranek, et al. Circulation 2013), prompting us to hypothesize that proteasome-priming may contribute to cardioprotection-induced by PDE5 inhibition. Here we used a cardiomyocyte-restricted proteasome inhibition transgenic mouse line (Tg) and non-Tg (Ntg) littermates to interrogate the action of sildenafil on I-R injury created by left anterior descending artery (LAD) ligation (30 min) and release (24 hr). Sildenafil was administered 30 min before LAD ligation. Results showed that (1) the 26S proteasome activity of the Ntg I-R hearts was significantly elevated by sildenafil but this elevation was blocked in the Tg line; (2) the infarct size reduction by sildenafil treatment in Ntg mice was completely abolished in the Tg mice with the same treatment; and (3) systolic and diastolic function impairment after I/R was markedly attenuated in sildenafil-treated Ntg mice, but not in the sildenafil-treated Tg mice. Additionally, immunoprecipitation assays show that PKG interacted with the proteasome in cultured cardiomyocytes, and this interaction appeared to be augmented by sildenafil treatment. Moreover, in vitro incubation of active PKG with purified human 26S proteasomes increased proteasome peptidase activities and the phosphorylation at specific serine residues of a 19S proteasome subunit as revealed by “gel-free” nano-LC-MS/MS. We conclude that active PKG directly interacts with, phosphorylates, and increases the activities of, the proteasome and that proteasome priming mediates to cardioprotection of PDE5 inhibition against I-R injury.

PDE5A inhibition attenuates bleomycin-induced pulmonary fibrosis and pulmonary hypertension through inhibition of ROS generation and RhoA/Rho kinase activation

2008 ◽  
Vol 294 (1) ◽  
pp. L24-L33 ◽  
Author(s):  
Anna R. Hemnes ◽  
Ari Zaiman ◽  
Hunter C. Champion
Keyword(s):  
Pulmonary Hypertension ◽  
Interstitial Lung Disease ◽  
Pulmonary Fibrosis ◽  
Right Ventricular ◽  
Lung Disease ◽  
Rho Kinase ◽  
Saline Control ◽  
Ros Generation ◽  
Pde5 Inhibition ◽  
Phosphodiesterase Type

Pulmonary hypertension frequently complicates interstitial lung disease, where it is associated with a high mortality. Patients with this dual diagnosis often fare worse than those with pulmonary arterial hypertension (PAH) alone and respond poorly to standard PAH therapy, often dying of right ventricular (RV) failure. We hypothesize that nitric oxide synthase (NOS) uncoupling is important in the pathogenesis of interstitial lung disease-associated pulmonary hypertension, and this process can be abrogated by phosphodiesterase type 5 (PDE5) inhibition to improve pulmonary vascular remodeling and right ventricular function. Intratracheal bleomycin (4 U/kg) or saline control was administered to C57/BL6 mice after anesthesia. After recovery, animals were fed a diet of sildenafil (100 mg·kg−1·day−1) or vehicle for 2 wk when they underwent hemodynamic measurements, and tissues were harvested. Survival was reduced in animals treated with bleomycin compared with controls and was improved with sildenafil (100.0 vs. 73.7 vs. 84.2%, P < 0.05). RV/LV+S ratio was higher in bleomycin-alone mice with improvement in ratio when sildenafil was administered (33.00 ± 0.01% vs. 20.98 ± 0.01% P < 0.05). Histology showed less pulmonary vascular and RV fibrosis in the group cotreated with sildenafil. Bleomycin was associated with a marked increase in superoxide generation by DHE histological staining and luminol activity in both heart and lung. Treatment with sildenafil resulted in a concomitant reduction in superoxide levels in both heart and lung. These data demonstrate that PDE5 inhibition ameliorates RV hypertrophy and pulmonary fibrosis associated with intratracheal bleomycin in a manner that is associated with improved NOS coupling and a reduction in reactive oxygen species signaling.

First Syntheses of Lorneic Acids A and B with Potential PDE5 Inhibition Activity

Synlett ◽  
2012 ◽  
Vol 23 (04) ◽  
pp. 607-610 ◽  
Author(s):  
Xiaochuan Chen ◽  
Xiang Ma ◽  
Yuting Song ◽  
Hao Liu ◽  
Ruijiao Chen
Keyword(s):  
Inhibition Activity ◽  
Pde5 Inhibition

scholarly journals Effect of PDE5 inhibition on the modulation of sympathetic α-adrenergic vasoconstriction in contracting skeletal muscle of young and older recreationally active humans

2015 ◽  
Vol 309 (11) ◽  
pp. H1867-H1875 ◽  
Author(s):  
Michael Nyberg ◽  
Peter Piil ◽  
Jon Egelund ◽  
Randy S. Sprague ◽  
Stefan P. Mortensen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Human Subjects ◽  
Pde5 Inhibitor ◽  
Knee Extensor ◽  
No Donor ◽  
Pde5 Inhibition ◽  
Exercise Hyperemia ◽  
Functional Sympatholysis ◽  
Venous Plasma

Aging is associated with an altered regulation of blood flow to contracting skeletal muscle; however, the precise mechanisms remain unclear. We recently demonstrated that inhibition of cGMP-binding phosphodiesterase 5 (PDE5) increased blood flow to contracting skeletal muscle of older but not young human subjects. Here we examined whether this effect of PDE5 inhibition was related to an improved ability to blunt α-adrenergic vasoconstriction (functional sympatholysis) and/or improved efficacy of local vasodilator pathways. A group of young (23 ± 1 yr) and a group of older (72 ± 1 yr) male subjects performed knee-extensor exercise in a control setting and following intake of the highly selective PDE5 inhibitor sildenafil. During both conditions, exercise was performed without and with arterial tyramine infusion to evoke endogenous norepinephrine release and consequently stimulation of α1- and α2-adrenergic receptors. The level of the sympatholytic compound ATP was measured in venous plasma by use of the microdialysis technique. Sildenafil increased ( P < 0.05) vascular conductance during exercise in the older group, but tyramine infusion reduced ( P < 0.05) this effect by 38 ± 9%. Similarly, tyramine reduced ( P < 0.05) the vasodilation induced by arterial infusion of a nitric oxide (NO) donor by 54 ± 9% in the older group, and this effect was not altered by sildenafil. Venous plasma [ATP] did not change with PDE5 inhibition in the older subjects during exercise. Collectively, PDE5 inhibition in older humans was not associated with an improved ability for functional sympatholysis. An improved efficacy of the NO system may be one mechanism underlying the effect of PDE5 inhibition on exercise hyperemia in aging.

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