Levels of l-arginine and l-citrulline in patients with erectile dysfunction of different etiology.
Nitric oxide is a physiologic signal essential to penile erection. l-citrulline (l-Cit) is converted into l-arginine (l-Arg), the precursor from which nitric oxide is generated. The level of l-Arg and l-Cit in the field of male sexual function remains relatively underexplored. The aim of the study was to evaluate the level of serum l-Arg and of l-Cit in a group of patients with erectile dysfunction. Diagnosis and severity of erectile dysfunction was based on the IIEF-5 and its etiology was classified as arteriogenic (A-ED), borderline (BL-ED), and non-arteriogenic (NA-ED) with penile echo-color-Doppler in basal condition and after intracaversous injection of prostaglandin E1. Serum l-Arg and l-Cit concentrations were measured by a cation-exchange chromatography system. l-Arg and l-Cit levels of men with A-ED were compared with those of male with BL-ED and NA-ED. Median level of l-Arg and l-Cit in 122 erectile dysfunction patients (41 A-ED, 23 ED-BL, 58 NA-ED) was 82.7 and 35.4 μmol/L, respectively. l-Arg and l-Cit levels in control patients were not significantly different (p = 0.233 and p = 0.561, respectively) than in total erectile dysfunction patients. l-Arg and l-Cit levels in control patients were significantly higher (p < 0.001 and p < 0.018, respectively) than in A-ED patients, but no difference (p > 0.50) was observed in controls and in both BL-ED and NA-ED patients. Patients with severe/complete-erectile dysfunction (IIEF-5 < 10) had l-Arg or l-Cit level significantly lower (-17%, p < 0.03; -13%, p < 0.04) and were more frequent (p < 0.01 and p < 0.04) under the respective median level (82.7 and 35.4 μmol/L) than those with mild-erectile dysfunction (IIEF-5 = 16-20). l-Arg and l-Cit levels in A-ED were significantly lower (p < 0.007 and p < 0.001, respectively) than in NA-ED patients. Penile echo-color-Doppler revealed that A-ED (peak systolic velocity ≤ 25 cm/sec) was more frequent in men with l-Arg under 82.7 μmol/L or l-Cit under 35.4 μmol/L and in the same population, the median peak systolic velocity values were lower in l-Arg deficient (29 vs. 35; p < 0.04) and also in l-Cit deficient (31 vs. 33, p > 0.3) but without reaching the statistical significance. Our study shows that a significant proportion of erectile dysfunction patients have low l-Arg or l-Cit level and that this condition is more frequent in patients with arteriogenic etiology. Low levels of these nitric oxide synthase substrates might increase the erectile dysfunction risk by reducing the concentration of nitric oxide.
Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milano, Italy.
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Barassi
Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milano, Italy.|Unità Operativa Medicina di Laboratorio -1 Patologia Clinica, IRCCS Policlinico San Donato, San Donato Milanese, Milano, Italy.
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Corsi Romanelli
Dipartimento di Malattie dell'Apparato Digerente e Medicina Interna, Ospedale Sant'Orsola-Malpighi, Alma Mater Studiorum, Università degli Studi di Bologna, Bologna, Italy.
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Pezzilli
Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milano, Italy.
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CA
Damele
ISES - Istituto per la Sterilità e la Sessualità, Milano, Italy.
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Vaccalluzzo
Dipartimento di Scienze Biomediche, Chirurgiche e Odontoiatriche, Università degli Studi di Milano, Milano, Italy.
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Goi
Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, Milano, Italy.
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Papini
ISES - Istituto per la Sterilità e la Sessualità, Milano, Italy.
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GM
Colpi
Dipartimento di Scienze Biomediche, Chirurgiche e Odontoiatriche, Università degli Studi di Milano, Milano, Italy.
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Massaccesi
Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milano, Italy.
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GV
Melzi d'Eril
D000328:Adult; D001120:Arginine / Q000097:blood*; D002956:Citrulline / Q000097:blood*; D007172:Erectile Dysfunction / Q000097:blood* / Q000000981:diagnostic imaging / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010410:Penile Erection / Q000502:physiology*; D012720:Severity of Illness Index; D018615:Ultrasonography, Doppler, Color
D002956:Citrulline; D001120:Arginine
erectile dysfunction; l-arginine; l-citrulline