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Phentolamine relaxes human corpus cavernosum by a nonadrenergic mechanism activating ATP-sensitive K+ channel

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Abstract

To investigate the pharmacodynamics of phentolamine in human corpus cavernosum (HCC) with special attention to the role of the K+ channels. Strips of HCC precontracted with nonadrenergic stimuli and kept in isometric organ bath immersed in a modified Krebs–Henseleit solution enriched with guanethidine and indomethacine were used in order to study the mechanism of the phentolamine-induced relaxation. Phentolamine caused relaxation (≈50%) in HCC strips precontracted with K+ 40 mM. This effect was not blocked by tetrodotoxin (1 μM) (54.6±4.6 vs 48.9±6.4%) or (atropine (10 μM) (52.7±6.5 vs 58.6±5.6%). However, this relaxation was significantly attenuated by L-NAME (100 μM) (59.7±5.8 vs 27.8±7.1%; P<0.05; n=8) and ODQ (100 μM) (62.7±5.1 vs 26.8±3.9%; P<0.05; n=8). Charybdotoxin and apamin (KCa-channel blockers) did not affect the phentolamine relaxations (54.6±4.6 vs 59.3±5.2%). Glibenclamide (100 μM), an inhibitor of KATP-channel, caused a significant inhibition (56.7±6.3 vs 11.3±2.3%; P<0.05; n=8) of the phentolamine-induced relaxation. In addition, the association of glibenclamide and L-NAME almost abolished the phentolamine-mediated relaxation (54.6±5.6 vs 5.7±1.4%; P<0.05; n=8). The results suggest that phentolamine relaxes HCC by a nonadrenergic–noncholinergic mechanism dependent on nitric oxide synthase activity and activation of KATP-channel.

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Authors and Affiliations

  1. Surgery Department, Federal University of Ceara, Fortaleza, Ceara, Brazil

    L F G Silva, M E Moraes, P R L Vasconcelos & M O Moraes

  2. Veterinary College, State University of Ceara, Fortaleza, Ceara, Brazil

    N R F Nascimento & M C Fonteles

  3. Department of Pharmacology, UNICAMP, Campinas, Brazil

    G de Nucci

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  1. L F G Silva
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  2. N R F Nascimento
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  3. M C Fonteles
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  4. G de Nucci
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  5. M E Moraes
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  6. P R L Vasconcelos
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  7. M O Moraes
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Correspondence to L F G Silva.

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Silva, L., Nascimento, N., Fonteles, M. et al. Phentolamine relaxes human corpus cavernosum by a nonadrenergic mechanism activating ATP-sensitive K+ channel. Int J Impot Res 17, 27–32 (2005). https://doi.org/10.1038/sj.ijir.3901269

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  • DOI: https://doi.org/10.1038/sj.ijir.3901269

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