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Erschienen in: World Journal of Urology 4/2011

01.08.2011 | Original Article

Functional inhibition of erectile process in rats by indomethacin

verfasst von: Amira M. Senbel

Erschienen in: World Journal of Urology | Ausgabe 4/2011

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Abstract

Objectives

Despite the important role played by prostaglandins in the control of erection, the potential contribution of non-steroidal anti-inflammatory drugs in erectile dysfunction in experimental animals has not been investigated. We examined the effect of the selective COX-2 inhibitor, celexocib, and the non-selective COX-inhibitors, indomethacin and diclofenac on erectile process in vivo.

Methods

Erectile responses to electrical stimulation of the cavernous nerve in anesthetized male rats were recorded after single and repeated administration and intracavernosal pressure/mean arterial pressure (ICP/MAP) was calculated. The effect on blood pressure during erection and total plasma nitrite/nitrate level was also investigated.

Results

Single-dose administration of indomethacin significantly reduced erectile responses to electrical stimulation at all frequencies tested; 15 mg/kg further reduced ICP/MAP to 0.016 ± 0.005 compared to 0.064 ± 0.012 and 0.104 ± 0.035 for indomethacin (5 mg/kg) and control, respectively at 0.5 Hz. Longer-term treatment with indomethacin completely abolished erectile responses at low frequencies and significantly reduced ICP/MAP at higher frequencies, accompanied by significant reduction in total plasma nitrite/nitrate level. Diclofenac reduced erectile responses only at low frequencies in contrast to celexocib that failed to negatively affect erectile responses.

Conclusion

Indomethacin, and to a lower extent diclofenac, may adversely affect erectile responses in rats.
Literatur
1.
Zurück zum Zitat Breivik H, Collett B, Ventafridda V, Cohen R, Gallacher D (2006) Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain 10:287–333PubMedCrossRef Breivik H, Collett B, Ventafridda V, Cohen R, Gallacher D (2006) Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain 10:287–333PubMedCrossRef
2.
Zurück zum Zitat Allison MC, Howatson AG, Torrance CJ, Lee FD, Russell RI (1992) Gastrointestinal damage associated with the use of nonsteroidal antiinflammatory drugs. N Engl J Med 327:749–754PubMedCrossRef Allison MC, Howatson AG, Torrance CJ, Lee FD, Russell RI (1992) Gastrointestinal damage associated with the use of nonsteroidal antiinflammatory drugs. N Engl J Med 327:749–754PubMedCrossRef
3.
Zurück zum Zitat Griffin MR, Yared A, Ray WA (2000) Nonsteroidal antiinflamatory drugs and acute renal failure in elderly persons. Am J Epidemiol 151:488–496PubMed Griffin MR, Yared A, Ray WA (2000) Nonsteroidal antiinflamatory drugs and acute renal failure in elderly persons. Am J Epidemiol 151:488–496PubMed
4.
Zurück zum Zitat Garcia Rodriguez LA, Hernandez-Diaz S (2003) Non-steroidal anti-inflammatory drugs as a trigger of clinical heart failure. Epidemiology 14:240–246PubMed Garcia Rodriguez LA, Hernandez-Diaz S (2003) Non-steroidal anti-inflammatory drugs as a trigger of clinical heart failure. Epidemiology 14:240–246PubMed
5.
Zurück zum Zitat Hernandez-Diaz S, Varas-Lorenzo C, Garcia Rodriguez LA (2006) Non-steroidal antiinflammatory drugs and the risk of acute myocardial infarction. Basic Clin Pharmacol Toxicol 98:266–274PubMedCrossRef Hernandez-Diaz S, Varas-Lorenzo C, Garcia Rodriguez LA (2006) Non-steroidal antiinflammatory drugs and the risk of acute myocardial infarction. Basic Clin Pharmacol Toxicol 98:266–274PubMedCrossRef
6.
Zurück zum Zitat Shiri R, Koskimäki J, Häkkinen J, Tammela TL, Auvinen A, Hakama M (2006) Effect of nonsteroidal anti-inflammatory drug use on the incidence of erectile dysfunction. J Urol 175(5):1812–1815PubMedCrossRef Shiri R, Koskimäki J, Häkkinen J, Tammela TL, Auvinen A, Hakama M (2006) Effect of nonsteroidal anti-inflammatory drug use on the incidence of erectile dysfunction. J Urol 175(5):1812–1815PubMedCrossRef
7.
Zurück zum Zitat Khan MA, Thompson CS, Sullivan ME, Jeremy JY, Mikhailidis DP, Morgan RJ (1999) The role of prostaglandins in the aetiology and treatment of erectile dysfunction. Prostaglandins Leukot Essent Fatty Acids 60:169–174PubMedCrossRef Khan MA, Thompson CS, Sullivan ME, Jeremy JY, Mikhailidis DP, Morgan RJ (1999) The role of prostaglandins in the aetiology and treatment of erectile dysfunction. Prostaglandins Leukot Essent Fatty Acids 60:169–174PubMedCrossRef
8.
Zurück zum Zitat Lee SW, Wang HZ, Zhao W, Ney P, Brink PR, Christ GJ (1999) Prostaglandin E1 activates the large-conductance KCa channel in human corporal smooth muscle cells. Int J Impot Res 11:189–199PubMedCrossRef Lee SW, Wang HZ, Zhao W, Ney P, Brink PR, Christ GJ (1999) Prostaglandin E1 activates the large-conductance KCa channel in human corporal smooth muscle cells. Int J Impot Res 11:189–199PubMedCrossRef
9.
Zurück zum Zitat Escrig A, Marin R, Mas M (1999) Repeated PGE1 treatment enhances nitric oxide and erection responses to nerve stimulation in the rat penis by upregulating constitutive NOS isoforms. J Urol 162:2205–2210PubMedCrossRef Escrig A, Marin R, Mas M (1999) Repeated PGE1 treatment enhances nitric oxide and erection responses to nerve stimulation in the rat penis by upregulating constitutive NOS isoforms. J Urol 162:2205–2210PubMedCrossRef
10.
Zurück zum Zitat Moreland RB, Traish A, McMillan MA, Smith B, Goldstein I, Saenz de Tejada I (1995) PGE1 suppresses the induction of collagen synthesis by transforming growth factor-1 in human corpus cavernosum smooth muscle. J Urol 153:826–834PubMedCrossRef Moreland RB, Traish A, McMillan MA, Smith B, Goldstein I, Saenz de Tejada I (1995) PGE1 suppresses the induction of collagen synthesis by transforming growth factor-1 in human corpus cavernosum smooth muscle. J Urol 153:826–834PubMedCrossRef
11.
Zurück zum Zitat Padma-Nathan H, Hellstrom WJ, Kaiser FE, Labasky RF, Lue TF, Nolten WE, Norwood PC, Peterson CA, Shabsigh R, Tam PY (1997) Treatment of men with erectile dysfunction with transurethral alprostadil. Medicated Urethral System for Erection (MUSE.) Study Group. N Engl J Med 336:1–7PubMedCrossRef Padma-Nathan H, Hellstrom WJ, Kaiser FE, Labasky RF, Lue TF, Nolten WE, Norwood PC, Peterson CA, Shabsigh R, Tam PY (1997) Treatment of men with erectile dysfunction with transurethral alprostadil. Medicated Urethral System for Erection (MUSE.) Study Group. N Engl J Med 336:1–7PubMedCrossRef
12.
Zurück zum Zitat Giuliano F, Bernabe J, Jardin A, Rousseau JP (1993) Antierectile role of the sympathetic nervous system in rats. J Urol 150:519–524PubMed Giuliano F, Bernabe J, Jardin A, Rousseau JP (1993) Antierectile role of the sympathetic nervous system in rats. J Urol 150:519–524PubMed
13.
Zurück zum Zitat Tseng CJ, Liu HY, Lin HC, Ger LP, Tung CS, Yen MH (1996) Cardiovascular effects of nitric oxide in the brain stem nuclei of rats. Hypertension 27:36–42PubMed Tseng CJ, Liu HY, Lin HC, Ger LP, Tung CS, Yen MH (1996) Cardiovascular effects of nitric oxide in the brain stem nuclei of rats. Hypertension 27:36–42PubMed
14.
Zurück zum Zitat Cosentino F, Hishikawa K, Katusic ZS, Luscher TF (1997) High glucose increases nitric oxide synthase expression and superoxide anion generation in human aortic endothelial cells. Circulation 96:25–28PubMed Cosentino F, Hishikawa K, Katusic ZS, Luscher TF (1997) High glucose increases nitric oxide synthase expression and superoxide anion generation in human aortic endothelial cells. Circulation 96:25–28PubMed
15.
Zurück zum Zitat Ignarro LJ, Bush PA, Buga GM, Wood KS, Fukuto JM, Rajfer J (1990) Nitric oxide and cyclic GMP formation upon electrical field stimulation cause relaxation of corpus cavernosum smooth muscle. Biochem Biophys Res Commun 170(2):843–850PubMedCrossRef Ignarro LJ, Bush PA, Buga GM, Wood KS, Fukuto JM, Rajfer J (1990) Nitric oxide and cyclic GMP formation upon electrical field stimulation cause relaxation of corpus cavernosum smooth muscle. Biochem Biophys Res Commun 170(2):843–850PubMedCrossRef
16.
Zurück zum Zitat Cuthbert AW, Wong PYD (1986) Electrogenic anion secretion in cultured rat epididymal epithelium. J Physiol 378:335–346PubMed Cuthbert AW, Wong PYD (1986) Electrogenic anion secretion in cultured rat epididymal epithelium. J Physiol 378:335–346PubMed
17.
Zurück zum Zitat Cheuk BLY, Leung PS, Lo ACT, Wong PYD (2000) Androgen control of cyclooxygenase expression in the rat epididymis. Biol Reprod 63:775–780PubMed Cheuk BLY, Leung PS, Lo ACT, Wong PYD (2000) Androgen control of cyclooxygenase expression in the rat epididymis. Biol Reprod 63:775–780PubMed
18.
Zurück zum Zitat Pérez-Torres I, El Hafidi M, Pavón N, Infante O, Avila-Casado MC, Baños G (2010) Effect of gonadectomy on the metabolism of arachidonic acid in isolated kidney of a rat model of metabolic syndrome. Metabolism 59(3):414–423PubMedCrossRef Pérez-Torres I, El Hafidi M, Pavón N, Infante O, Avila-Casado MC, Baños G (2010) Effect of gonadectomy on the metabolism of arachidonic acid in isolated kidney of a rat model of metabolic syndrome. Metabolism 59(3):414–423PubMedCrossRef
19.
Zurück zum Zitat Argiolas A, Melis MR, Stancampiano R, Gessa GL (1990) Oxytocin-induced penile erection and yawning: role of calcium and prostaglandins. Pharmacol Biochem Behav 35(3):601–605PubMedCrossRef Argiolas A, Melis MR, Stancampiano R, Gessa GL (1990) Oxytocin-induced penile erection and yawning: role of calcium and prostaglandins. Pharmacol Biochem Behav 35(3):601–605PubMedCrossRef
20.
Zurück zum Zitat Maneiro E, López-Armada MJ, Fernández-Sueiro JL, Lema B, Galdo F, Blanco FJ (2001) Aceclofenac increases the synthesis of interleukin 1 receptor antagonist and decreases the production of nitric oxide in human articular chondrocytes. J Rheumatol 28(12):2692–2699PubMed Maneiro E, López-Armada MJ, Fernández-Sueiro JL, Lema B, Galdo F, Blanco FJ (2001) Aceclofenac increases the synthesis of interleukin 1 receptor antagonist and decreases the production of nitric oxide in human articular chondrocytes. J Rheumatol 28(12):2692–2699PubMed
21.
Zurück zum Zitat McKanna JA, Zhang MZ, Wang JL, Cheng HF, Harris RC (1998) Constitutive expression of cyclooxygenase-2 in rat vas deferens. Am J Physiol 275((1 Pt 2)):R227–R233PubMed McKanna JA, Zhang MZ, Wang JL, Cheng HF, Harris RC (1998) Constitutive expression of cyclooxygenase-2 in rat vas deferens. Am J Physiol 275((1 Pt 2)):R227–R233PubMed
22.
Zurück zum Zitat Iimoto S, Watanabe S, Takahashi T, Shimizu A, Yamamoto H (2005) The influence of celecoxib on matrix synthesis by chondrocytes under mechanical stress in vitro. Int J Mol Med 16(6):1083–1088PubMed Iimoto S, Watanabe S, Takahashi T, Shimizu A, Yamamoto H (2005) The influence of celecoxib on matrix synthesis by chondrocytes under mechanical stress in vitro. Int J Mol Med 16(6):1083–1088PubMed
23.
Zurück zum Zitat O’Banion MK (1999) Cyclooxygenase-2: molecular biology, pharmacology and neurobiology. Crit Rev Neurobiol 13:45–82PubMed O’Banion MK (1999) Cyclooxygenase-2: molecular biology, pharmacology and neurobiology. Crit Rev Neurobiol 13:45–82PubMed
24.
Zurück zum Zitat Langworthy OR (1965) Innervation of the pelvic organs of the rat. Invest Urol 2:491–495PubMed Langworthy OR (1965) Innervation of the pelvic organs of the rat. Invest Urol 2:491–495PubMed
25.
Zurück zum Zitat Quinlan DM, Nelson RJ, Partin AW, Mostwin JL, Walsh PC (1989) The rat as a model for the study of penile erection. J Urol 141:656–661PubMed Quinlan DM, Nelson RJ, Partin AW, Mostwin JL, Walsh PC (1989) The rat as a model for the study of penile erection. J Urol 141:656–661PubMed
26.
Zurück zum Zitat Hulsebosch CE, Coggeshall RE (1982) An analysis of the axon populations in the nerves of the pelvic viscera in the rat. J Comp Neurol 211:1–6PubMedCrossRef Hulsebosch CE, Coggeshall RE (1982) An analysis of the axon populations in the nerves of the pelvic viscera in the rat. J Comp Neurol 211:1–6PubMedCrossRef
27.
Zurück zum Zitat Chen K, Chan JH, Chang LS, Chen M, Chan S (1992) Intracavernous pressure as an experimental index in a rat model for the evaluation of penile erection. J Urol 147:1124–1128PubMed Chen K, Chan JH, Chang LS, Chen M, Chan S (1992) Intracavernous pressure as an experimental index in a rat model for the evaluation of penile erection. J Urol 147:1124–1128PubMed
28.
Zurück zum Zitat Gray GD, Smith ER, Dorsa DM, Davidson JM (1981) Sexual behavior and testosterone in middle-aged male rats. Endocrinology 109:1597–1602PubMedCrossRef Gray GD, Smith ER, Dorsa DM, Davidson JM (1981) Sexual behavior and testosterone in middle-aged male rats. Endocrinology 109:1597–1602PubMedCrossRef
29.
Zurück zum Zitat Bornman MS, Franz RC, Jacobs DJ, Du Plessis DJ (1987) Effect of single dose aspirin on the development of penile hypercoagulability during erection. Br J Urol 59(3):267–271PubMedCrossRef Bornman MS, Franz RC, Jacobs DJ, Du Plessis DJ (1987) Effect of single dose aspirin on the development of penile hypercoagulability during erection. Br J Urol 59(3):267–271PubMedCrossRef
30.
Zurück zum Zitat Nishio E, Watanabe Y (1998) Aspirin and salicylate enhances the induction of inducible nitric oxide synthase in cultured rat smooth muscle cells. Life Sci 63(6):429–439PubMedCrossRef Nishio E, Watanabe Y (1998) Aspirin and salicylate enhances the induction of inducible nitric oxide synthase in cultured rat smooth muscle cells. Life Sci 63(6):429–439PubMedCrossRef
Metadaten
Titel
Functional inhibition of erectile process in rats by indomethacin
verfasst von
Amira M. Senbel
Publikationsdatum
01.08.2011
Verlag
Springer-Verlag
Erschienen in
World Journal of Urology / Ausgabe 4/2011
Print ISSN: 0724-4983
Elektronische ISSN: 1433-8726
DOI
https://doi.org/10.1007/s00345-010-0600-0

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