Increased cyclic guanosine monophosphate production and endothelial nitric oxide synthase level in mononuclear cells from sildenafil citrate-treated patients with erectile dysfunction.
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.
García-Cardoso
J
J
Department of Urology, Fundación Jiménez Díaz, Madrid, Spain.
Vela
R
R
Mahillo
E
E
Mateos-Cáceres
P J
PJ
Modrego
J
J
Macaya
C
C
López-Farré
A J
AJ
D000368:Aged; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000378:metabolism; D007172:Erectile Dysfunction / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006157:Guanosine Monophosphate / Q000096:biosynthesis*; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D018783:Impotence, Vasculogenic / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000201:enzymology / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D011687:Purines / Q000494:pharmacology / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology* / Q000627:therapeutic use
D002097:C-Reactive Protein; D002784:Cholesterol; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D006442:Glycated Hemoglobin; D006157:Guanosine Monophosphate; D006162:Guanylate Cyclase; D018799:Intercellular Adhesion Molecule-1; D052250:Nitric Oxide Synthase Type III; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones