Increased cyclic guanosine monophosphate production and endothelial nitric oxide synthase level in mononuclear cells from sildenafil citrate-treated patients with erectile dysfunction

• Published in: International journal of impotence research Vol. 22; no. 1; pp. 68 - 76
• Main Authors: García-Cardoso, J, Vela, R, Mahillo, E, Mateos-Cáceres, P J, Modrego, J, Macaya, C, López-Farré, A J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-01-2010; Nature Publishing Group
• Subjects: Aged; Biological and medical sciences; Body Mass Index; C-reactive protein; C-Reactive Protein - metabolism; Care and treatment; Cholesterol - blood; Cyclic guanylic acid; Cyclic Nucleotide Phosphodiesterases, Type 5 - metabolism; Erectile dysfunction; Erectile Dysfunction - drug therapy; Erectile Dysfunction - enzymology; Erectile Dysfunction - metabolism; Glycated Hemoglobin A - metabolism; Guanosine Monophosphate - biosynthesis; Guanylate Cyclase - metabolism; Gynecology. Andrology. Obstetrics; Health aspects; Humans; Impotence; Impotence, Vasculogenic - drug therapy; Impotence, Vasculogenic - enzymology; Impotence, Vasculogenic - metabolism; Intercellular Adhesion Molecule-1 - blood; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Monocytes - enzymology; Monocytes - metabolism; Nitric oxide; Nitric Oxide Synthase Type III - metabolism; original-article; Phosphodiesterase Inhibitors - pharmacology; Phosphodiesterase Inhibitors - therapeutic use; Physiological aspects; Piperazines - pharmacology; Piperazines - therapeutic use; Proteins; Purines - pharmacology; Purines - therapeutic use; Reproductive Medicine; Risk factors; rology; Sildenafil; Sildenafil Citrate; Sulfones - pharmacology; Sulfones - therapeutic use; Urology; Spain; sICAM-1; PDE5 inhibitors; NO/cGMP system; hs-CRP; erectile dysfunction; Andrology; Vasodilator agent; 3',5'-Cyclic-GMP phosphodiesterase; Esterases; Biosynthesis; Phosphoric diester hydrolases; Mononuclear cell; Male genital diseases; Human; Erection disorders; Enzyme; Enzyme inhibitor; 3',5'-GMP; Nitric-oxide synthase; Phosphodiesterase 5 inhibitor; Phosphodiesterase inhibitor; Treatment; Hydrolases; Oxidoreductases; Sildenafil
• ISSN: 0955-9930; 1476-5489
• DOI: 10.1038/ijir.2009.51

Mononuclear cells express enzymes involved in the NO/cyclic guanosine monophosphate (cGMP) generating system, as well as PDE5. The objective of the study was to determine the effect of sildenafil citrate administration on the level of proteins involved in the NO/cGMP generating system in mononuclear cells from patients with ED. Twenty-one patients with ED (International Index of Erectile Function-Erectile Function Domain (IIEF-EFD) 17.9±0.8) were enrolled and 100 mg sildenafil citrate on-demand was administered during 12 weeks. All patients showed cardiovascular risk factors. After sildenafil citrate administration, IIEF-EFD score was improved (26±1.2
P
<0.05). In the mononuclear cells, the protein level of endothelial NO synthase (eNOS) was higher after sildenafil citrate treatment. It was accompanied by reduction in the circulating plasma levels of both high-sensitive C-reactive protein and soluble intercellular adhesive molecule-1. The protein level of soluble guanylate cyclase and PDE5 did not change in the mononuclear cells after sildenafil citrate treatment. However, in the mononuclear cells exogenous NO induced a higher cGMP production after 12-weeks sildenafil citrate administration. In conclusion, in mononuclear cells from patients with ED sildenafil citrate administration increased the level of eNOS protein and increased cGMP production in response to NO. Moreover, sildenafil citrate administration reduced the plasma circulating levels of two biomarkers associated with inflammation.