Abstract
Erectile dysfunctions are not uncommon, especially in patients suffering from metabolic syndrome and from a number of circulatory and psychiatric problems. cGMP diesterase inhibitors, such as sildenafil, have proven to be beneficial in the treatment of many such conditions. Our patients, all of them complaining of erectile dysfunction, were treated with sildenafil (50 mg, thrice a week for 6 weeks). All patients reported beneficial effects and were not clinically distinguishable (interview and Doppler scores). We sampled blood for systemic circulation (cubital vein) and from penis (corpora cavernosa) before and after prolonged sildenafil treatment, and measured nitrate (+nitrite) levels in plasma and in red blood cells (RBCs). Hemoglobin is a powerful catalyst of NO oxidation to nitrate, and we thought that nitrate in RBC might be a more sensitive parameter than plasma nitrate. We found that the ratio of penile vs systemic blood plasma nitrate was similar in all patients before or after sildenafil treatment. On the other hand, the same parameter measured in RBC showed that, at the beginning of treatment, patients could be divided into two groups: one with a high ratio and the other with a low ratio. Therefore, clinically similar patients could be biochemically divided into two populations. The difference disappeared after treatment, thus hinting at a curative effect of the drug. The mechanisms underlying this behavior are still unknown and the clinical implication of two populations that can be distinguished by RBC nitrate is yet to be evaluated.
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References
Gillies HC, Roblin D, Jackson G . Coronary and systemic hemodynamic effects of sildenafil citrate: from basic science to clinical studies in patients with cardiovascular disease. Int J Cardiol 2002; 86: 131–141.
Burnett AL . Nitric oxide in the penis: physiology and pathology. J Urol 1997; 157: 320–324.
Simonsen U, Prieto D, Delgado JA, Hernandez M, Resel L, Saenz dTI et al. Nitric oxide is involved in the inhibitory neurotransmission and endothelium-dependent relaxations of human small penile arteries. Clin Sci (Lond) 1997; 92: 269–275.
Agarwal A, Nandipati KC, Sharma RK, Zippe CD, Raina R . Role of oxidative stress in the pathophysiological mechanism of erectile dysfunction. J Androl 2006; 27: 335–347.
Seftel AD, Sun P, Swindle R . The prevalence of hypertension, hyperlipidemia, diabetes mellitus and depression in men with erectile dysfunction. J Urol 2004; 171: 2341–2345.
Radi R, Beckman JS, Bush KM, Freeman BA . Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide. Arch Biochem Biophys 1991; 288: 481–487.
Katusic ZS, Vanhoutte PM . Superoxide anion is an endothelium-derived contracting factor. Am J Physiol 1989; 257: H33–H37.
Beckman JS . Oxidative damage and tyrosine nitration from peroxynitrite. Chem Res Toxicol 1996; 9: 836–844.
Beckman JS, Koppenol WH . Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol 1996; 271: C1424–C1437.
Khan MA, Thompson CS, Mumtaz FH, Mikhailidis DP, Morgan RJ, Bruckdorfer RK et al. The effect of nitric oxide and peroxynitrite on rabbit cavernosal smooth muscle relaxation. World J Urol 2001; 19: 220–224.
Ballard SA, Gingell CJ, Tang K, Turner LA, Price ME, Naylor AM . Effects of sildenafil on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes. J Urol 1998; 159: 2164–2171.
Sommer F, Schulze W . Treating erectile dysfunction by endothelial rehabilitation with phosphodiesterase 5 inhibitors. World J Urol 2005; 23: 385–392.
Mathers MJ, Klotz T, Brandt AS, Roth S, Sommer F . Long-term treatment of erectile dysfunction with a phosphodiesterase-5 inhibitor and dose optimization based on nocturnal penile tumescence. BJU Int 2008; 101: 1129–1134.
Rosano GM, Aversa A, Vitale C, Fabbri A, Fini M, Spera G . Chronic treatment with tadalafil improves endothelial function in men with increased cardiovascular risk. Eur Urol 2005; 47: 214–220.
Montorsi F, Briganti A, Salonia A, Rigatti P, Burnett AL . Can phosphodiesterase type 5 inhibitors cure erectile dysfunction? Eur Urol 2006; 49: 979–986.
Rosen RC, Riley A, Wagner G, Osterloh IH, Kirkpatrick J, Mishra A . The international index of erectile function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology 1997; 49: 822–830.
Palmerini CA, Arienti G, Palombari R . Electrochemical determination of nitric oxide and of its derivatives. Talanta 2003; 61: 37–41.
Antonini E, Brunori M . Hemoglobin and Myoglobin in their Reactions with Ligands. North Holland: Amsterdam, 1971, pp 1–436.
Eich RF, Li T, Lemon DD, Doherty DH, Curry SR, Aitken JF et al. Mechanism of NO-induced oxidation of myoglobin and hemoglobin. Biochemistry 1996; 35: 6976–6983.
Pannala AS, Mani AR, Spencer JP, Skinner V, Bruckdorfer KR, Moore KP et al. The effect of dietary nitrate on salivary, plasma, and urinary nitrate metabolism in humans. Free Radic Biol Med 2003; 34: 576–584.
Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR . Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids. Anal Biochem 1982; 126: 131–138.
Becker AJ, Uckert S, Tsikas D, Noack H, Stief CG, Frolich JC et al. Determination of nitric oxide metabolites by means of the Griess assay and gas chromatography-mass spectrometry in the cavernous and systemic blood of healthy males and patients with erectile dysfunction during different functional conditions of the penis. Urol Res 2000; 28: 364–369.
DeSouza C, Parulkar A, Lumpkin D, Akers D, Fonseca VA . Acute and prolonged effects of sildenafil on brachial artery flow-mediated dilatation in type 2 diabetes. Diabetes Care 2002; 25: 1336–1339.
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Palmerini, C., Zucchi, A., Fioretti, F. et al. Erectile dysfunction and NO: variations of NO penile blood levels before and after sildenafil treatment. Int J Impot Res 21, 321–325 (2009). https://doi.org/10.1038/ijir.2009.33
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DOI: https://doi.org/10.1038/ijir.2009.33