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British journal of pharmacology1995; 116(6); 2582-2590; doi: 10.1111/j.1476-5381.1995.tb17211.x

Involvement of nitric oxide in the non-adrenergic non-cholinergic neurotransmission of horse deep penile arteries: role of charybdotoxin-sensitive K(+)-channels.

Abstract: 1. The involvement of nitric oxide (NO) and the signal transduction mechanisms mediating neurogenic relaxations were investigated in deep intracavernous penile arteries with an internal lumen diameter of 600-900 microns, isolated from the corpus cavernosum of young horses. 2. The presence of nitric oxide synthase (NOS)-positive nerves was examined in cross and longitudinal sections of isolated penile arteries processed for NADPH-diaphorase (NADPH-d) histochemistry. NADPH-d-positive nerve fibres were observed in the adventitia-media junction of deep penile arteries and in relation to the trabecular smooth muscle. 3. Electrical field stimulation (EFS) evoked frequency-dependent relaxations of both endothelium-intact and denuded arterial preparations treated with guanethidine (10(-5) M) and atropine (10(-7) M), and contracted with 10(-6) M phenylephrine. These EFS-induced relaxations were tetrodotoxin-sensitive indicating their non-adrenergic non-cholinergic (NANC) neurogenic origin. 4. EFS-evoked relaxations were abolished at the lowest frequency (0.5-2 Hz) and attenuated at higher frequencies (4-32 Hz) by the NOS inhibitor, NG-nitro-L-arginine (L-NOARG, 3 x 10(-3) M). This inhibitory effect was antagonized by the NO precursor, L-arginine (3 x 10(-3) M). NG-nitro-D-arginine (10(-4) M) did not affect the relaxations to EFS. 5. Incubation with either the NO scavenger, oxyhaemoglobin (10(-5) M), or methylene blue (10(-5) M), an inhibitor of guanylate cyclase activation by NO, caused significant inhibitions of the EFS-evoked relaxations, and while oxyhaemoglobin abolished the relaxations to exogenously added NO (acidified sodium nitrite, 10(-6) - 10(-3) M), there still persisted a relaxation to NO of 24.4 +/- 5.1% (n = 6) in the presence of methylene blue. 6. Glibenclamide (3 x 10(-6) M), an inhibitor of ATP-activated K(+)-channels, did not alter the relaxations to either EFS-stimulation or NO, while the blocker of Ca(2+)-activated K(+)-channels, charybdotoxin (3 x 10(-8) M), caused a significant inhibition of both the electrically-induced relaxations and the relaxations to exogenously added NO. Furthermore, charybdotoxin blocked relaxations induced by the cell permeable analogue of cyclic GMP, 8-bromo cyclic GMP (8 Br-cyclic GMP). 7. These results suggest that relaxations of horse deep penile arteries induced by NANC nerve stimulation involve mainly NO or a NO-like substance from nitrergic nerves. NO would stimulate the accumulation of cyclic GMP followed by increases in the open probability of Ca(2+)-activated K(+)-channels and hyperpolarization leading to relaxation of horse penile arteries.
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Publication Date: 1995-11-01 PubMed ID: 8590974PubMed Central: PMC1909130DOI: 10.1111/j.1476-5381.1995.tb17211.xGoogle Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research paper investigates the role of nitric oxide in the neurogenic relaxation of deep penile arteries in young horses, specifically focusing on charybdotoxin-sensitive K(+)-channels.

Experiment and Procedure

  • The study focuses on deep intracavernous penile arteries isolated from the corpus cavernosum in horses. The researchers explored the relation between nitric oxide (NO) and signal transduction mechanisms accountable for neurogenic relaxations.
  • Researchers looked for the presence of nitric oxide synthase (NOS)-positive nerves in the isolated penile arteries through NADPH-diaphorase (NADPH-d) histochemistry. Such NADPH-d-positive nerve fibers were spotted at the junction of the adventitia-media in the deep penile arteries and in relation to the trabecular smooth muscle.
  • Electrical Field Stimulation (EFS) brought about frequency-dependent relaxations of both endothelium-intact and denuded arterial preparations that were treated with guanethidine and atropine, and contracted with phenylephrine.

Nitric Oxide’s Role

  • EFS-evoked relaxations were removed at the lowest frequency and attenuated at higher frequencies by the NOS inhibitor, NG-nitro-L-arginine (L-NOARG).
  • Incubation with either the NO scavenger, oxyhaemoglobin, or methylene blue led to substantial inhibitions of the EFS-evoked relaxations.
  • Oxyhaemoglobin abolished relaxations to externally added NO, but a relaxation to NO of around 24.4 +/- 5.1% still persisted even in the presence of methylene blue.

Role of K(+)-channels

  • Glibenclamide, an inhibitor of ATP-activated K(+)-channels, had no impact on EFS-stimulations or NO-related relaxations. However, the blocker of Ca(2+)-activated K(+)-channels, charybdotoxin, led to significant inhibition of both the electrically-induced and NO-induced relaxations.
  • Charybdotoxin also blocked relaxations that were induced by the cell-permeable analogue of cyclic GMP, 8-bromo cyclic GMP.

Conclusion of Study

  • The study concluded that relaxations of horse deep penile arteries stimulated by non-adrenergic non-cholinergic (NANC) nerves primarily involve either NO or a NO-like substance from nitrergic nerves.
  • No would promote the accumulation of cyclic GMP leading to increases in the open probability of Ca(2+)-activated K(+)-channels and hyperpolarization. This ultimately results in the relaxation of horse penile arteries.

Cite This Article

APA
Simonsen U, Prieto D, Sánez de Tejada I, García-Sacristán A. (1995). Involvement of nitric oxide in the non-adrenergic non-cholinergic neurotransmission of horse deep penile arteries: role of charybdotoxin-sensitive K(+)-channels. Br J Pharmacol, 116(6), 2582-2590. https://doi.org/10.1111/j.1476-5381.1995.tb17211.x

Publication

British journal of pharmacology
ISSN: 0007-1188
NlmUniqueID: 7502536
Country: England
Language: English
Volume: 116
Issue: 6
Pages: 2582-2590

Researcher Affiliations

Simonsen, U
  • Departamento de Fisiologia, Facultad de Veterinaria, Universidad Complutense, Madrid, Spain.
Prieto, D
    Sánez de Tejada, I
      García-Sacristán, A

        MeSH Terms

        • Adrenergic Fibers / drug effects
        • Adrenergic Fibers / enzymology
        • Adrenergic Fibers / physiology
        • Animals
        • Arginine / analogs & derivatives
        • Arginine / pharmacology
        • Arginine / physiology
        • Charybdotoxin / pharmacology
        • Cholinergic Fibers / drug effects
        • Cholinergic Fibers / enzymology
        • Cholinergic Fibers / physiology
        • Electric Stimulation
        • Endothelium, Vascular / drug effects
        • Endothelium, Vascular / enzymology
        • Endothelium, Vascular / innervation
        • Glyburide / pharmacology
        • Horses
        • Male
        • Methylene Blue / pharmacology
        • Muscle Relaxation / drug effects
        • Muscle Relaxation / physiology
        • Muscle, Smooth, Vascular / drug effects
        • Muscle, Smooth, Vascular / enzymology
        • Muscle, Smooth, Vascular / innervation
        • NADPH Dehydrogenase / metabolism
        • Nerve Fibers / drug effects
        • Nerve Fibers / enzymology
        • Nerve Fibers / physiology
        • Nitric Oxide / physiology
        • Nitroarginine
        • Oxyhemoglobins / pharmacology
        • Penis / blood supply
        • Penis / drug effects
        • Potassium Channels / drug effects
        • Potassium Channels / physiology
        • Sensitivity and Specificity
        • Signal Transduction / drug effects
        • Signal Transduction / physiology
        • Synaptic Transmission / drug effects
        • Synaptic Transmission / physiology

        Grant Funding

        • DK-40487 / NIDDK NIH HHS
        • R01-DK-39080 / NIDDK NIH HHS

        References

        This article includes 47 references
        1. Burnett AL, Tillman SL, Chang TS, Epstein JI, Lowenstein CJ, Bredt DS, Snyder SH, Walsh PC. Immunohistochemical localization of nitric oxide synthase in the autonomic innervation of the human penis.. J Urol 1993 Jul;150(1):73-6.
          pubmed: 7685426doi: 10.1016/s0022-5347(17)35401-0google scholar: lookup
        2. Finberg JP, Levy S, Vardi Y. Inhibition of nerve stimulation-induced vasodilatation in corpora cavernosa of the pithed rat by blockade of nitric oxide synthase.. Br J Pharmacol 1993 Apr;108(4):1038-42.
          pubmed: 7683562doi: 10.1111/j.1476-5381.1993.tb13502.xgoogle scholar: lookup
        3. Robertson BE, Schubert R, Hescheler J, Nelson MT. cGMP-dependent protein kinase activates Ca-activated K channels in cerebral artery smooth muscle cells.. Am J Physiol 1993 Jul;265(1 Pt 1):C299-303.
          pubmed: 8338137doi: 10.1152/ajpcell.1993.265.1.C299google scholar: lookup
        4. Matsumoto T, Nakane M, Pollock JS, Kuk JE, Förstermann U. A correlation between soluble brain nitric oxide synthase and NADPH-diaphorase activity is only seen after exposure of the tissue to fixative.. Neurosci Lett 1993 May 28;155(1):61-4.
          pubmed: 7689718doi: 10.1016/0304-3940(93)90673-9google scholar: lookup
        5. Cowan CL, Palacino JJ, Najibi S, Cohen RA. Potassium channel-mediated relaxation to acetylcholine in rabbit arteries.. J Pharmacol Exp Ther 1993 Sep;266(3):1482-9.
          pubmed: 8396636
        6. Persico P, Calignano A, Mancuso F, Sorrentino L. Involvement of NK receptors and beta-adrenoceptors in nitric oxide-dependent relaxation of rabbit aorta rings following electrical-field stimulation.. Eur J Pharmacol 1993 Jul 6;238(1):105-9.
          pubmed: 7691617doi: 10.1016/0014-2999(93)90512-ggoogle scholar: lookup
        7. De Man JG, Boeckxstaens GE, Pelckmans PP, De Winter BY, Herman AG, Van Maercke YM. Prejunctional modulation of the nitrergic innervation of the canine ileocolonic junction via potassium channels.. Br J Pharmacol 1993 Oct;110(2):559-64.
          pubmed: 8242230doi: 10.1111/j.1476-5381.1993.tb13847.xgoogle scholar: lookup
        8. Khan SA, Mathews WR, Meisheri KD. Role of calcium-activated K+ channels in vasodilation induced by nitroglycerine, acetylcholine and nitric oxide.. J Pharmacol Exp Ther 1993 Dec;267(3):1327-35.
          pubmed: 7505330
        9. Hedlund P, Holmquist F, Hedlund H, Andersson KE. Effects of nicorandil on human isolated corpus cavernosum and cavernous artery.. J Urol 1994 Apr;151(4):1107-13.
          pubmed: 8126802doi: 10.1016/s0022-5347(17)35193-5google scholar: lookup
        10. Bolotina VM, Najibi S, Palacino JJ, Pagano PJ, Cohen RA. Nitric oxide directly activates calcium-dependent potassium channels in vascular smooth muscle.. Nature 1994 Apr 28;368(6474):850-3.
          pubmed: 7512692doi: 10.1038/368850a0google scholar: lookup
        11. Gustafsson LE, Persson MG, Wei SZ, Wiklund NP, Elias Y. Neurogenic vasodilation in rabbit hindlimb mediated by tachykinins and nitric oxide.. J Cardiovasc Pharmacol 1994 Apr;23(4):612-7.
          pubmed: 7516011doi: 10.1097/00005344-199404000-00013google scholar: lookup
        12. Vanheel B, Van de Voorde J, Leusen I. Contribution of nitric oxide to the endothelium-dependent hyperpolarization in rat aorta.. J Physiol 1994 Mar 1;475(2):277-84.
          pubmed: 8021834doi: 10.1113/jphysiol.1994.sp020068google scholar: lookup
        13. Vizzard MA, Erdman SL, Förstermann U, de Groat WC. Differential distribution of nitric oxide synthase in neural pathways to the urogenital organs (urethra, penis, urinary bladder) of the rat.. Brain Res 1994 May 23;646(2):279-91.
          pubmed: 7520823doi: 10.1016/0006-8993(94)90090-6google scholar: lookup
        14. Goulding EH, Tibbs GR, Siegelbaum SA. Molecular mechanism of cyclic-nucleotide-gated channel activation.. Nature 1994 Nov 24;372(6504):369-74.
          pubmed: 7969497doi: 10.1038/372369a0google scholar: lookup
        15. Klinge E, Sjöstrand NO. Contraction and relaxation of the retractor penis muscle and the penile artery of the bull.. Acta Physiol Scand Suppl 1974;420:1-88.
          pubmed: 4533582
        16. Larsson LI. Occurrence of nerves containing vasoactive intestinal polypeptide immunoreactivity in the male genital tract.. Life Sci 1977 Aug 15;21(4):503-8.
          pubmed: 20541doi: 10.1016/0024-3205(77)90088-1google scholar: lookup
        17. Craven PA, DeRubertis FR. Restoration of the responsiveness of purified guanylate cyclase to nitrosoguanidine, nitric oxide, and related activators by heme and hemeproteins. Evidence for involvement of the paramagnetic nitrosyl-heme complex in enzyme activation.. J Biol Chem 1978 Dec 10;253(23):8433-43.
          pubmed: 30778
        18. McConnell J, Benson GS, Wood J. Autonomic innervation of the mammalian penis: a histochemical and physiological study.. J Neural Transm 1979;45(3):227-38.
          pubmed: 113505doi: 10.1007/BF01244411google scholar: lookup
        19. Wallenstein S, Zucker CL, Fleiss JL. Some statistical methods useful in circulation research.. Circ Res 1980 Jul;47(1):1-9.
          pubmed: 7379260doi: 10.1161/01.res.47.1.1google scholar: lookup
        20. Gruetter CA, Kadowitz PJ, Ignarro LJ. Methylene blue inhibits coronary arterial relaxation and guanylate cyclase activation by nitroglycerin, sodium nitrite, and amyl nitrite.. Can J Physiol Pharmacol 1981 Feb;59(2):150-6.
          pubmed: 6112057doi: 10.1139/y81-025google scholar: lookup
        21. Polak JM, Gu J, Mina S, Bloom SR. Vipergic nerves in the penis.. Lancet 1981 Aug 1;2(8240):217-9.
          pubmed: 6114280doi: 10.1016/s0140-6736(81)90471-2google scholar: lookup
        22. Willis E, Ottesen B, Wagner G, Sundler F, Fahrenkrug J. Vasoactive intestinal polypeptide (VIP) as a possible neurotransmitter involved in penile erection.. Acta Physiol Scand 1981 Dec;113(4):545-7.
          pubmed: 7348038doi: 10.1111/j.1748-1716.1981.tb06936.xgoogle scholar: lookup
        23. Bowman A, Gillespie JS. Neurogenic vasodilatation in isolated bovine and canine penile arteries.. J Physiol 1983 Aug;341:603-16.
          pubmed: 6684686doi: 10.1113/jphysiol.1983.sp014827google scholar: lookup
        24. Andersson PO, Bloom SR, Mellander S. Haemodynamics of pelvic nerve induced penile erection in the dog: possible mediation by vasoactive intestinal polypeptide.. J Physiol 1984 May;350:209-24.
          pubmed: 6747850doi: 10.1113/jphysiol.1984.sp015197google scholar: lookup
        25. Martin W, Villani GM, Jothianandan D, Furchgott RF. Selective blockade of endothelium-dependent and glyceryl trinitrate-induced relaxation by hemoglobin and by methylene blue in the rabbit aorta.. J Pharmacol Exp Ther 1985 Mar;232(3):708-16.
          pubmed: 2983068
        26. Brindley GS. Pilot experiments on the actions of drugs injected into the human corpus cavernosum penis.. Br J Pharmacol 1986 Mar;87(3):495-500.
          pubmed: 3801762doi: 10.1111/j.1476-5381.1986.tb10191.xgoogle scholar: lookup
        27. Lue TF, Tanagho EA. Physiology of erection and pharmacological management of impotence.. J Urol 1987 May;137(5):829-36.
          pubmed: 3553617doi: 10.1016/s0022-5347(17)44267-4google scholar: lookup
        28. Juenemann KP, Lue TF, Luo JA, Jadallah SA, Nunes LL, Tanagho EA. The role of vasoactive intestinal polypeptide as a neurotransmitter in canine penile erection: a combined in vivo and immunohistochemical study.. J Urol 1987 Oct;138(4):871-7.
          pubmed: 2888903doi: 10.1016/s0022-5347(17)43406-9google scholar: lookup
        29. Saenz de Tejada I, Blanco R, Goldstein I, Azadzoi K, de las Morenas A, Krane RJ, Cohen RA. Cholinergic neurotransmission in human corpus cavernosum. I. Responses of isolated tissue.. Am J Physiol 1988 Mar;254(3 Pt 2):H459-67.
          pubmed: 2894778doi: 10.1152/ajpheart.1988.254.3.H459google scholar: lookup
        30. Hope BT, Vincent SR. Histochemical characterization of neuronal NADPH-diaphorase.. J Histochem Cytochem 1989 May;37(5):653-61.
          pubmed: 2703701doi: 10.1177/37.5.2703701google scholar: lookup
        31. Stief C, Benard F, Bosch R, Aboseif S, Nunes L, Lue TF, Tanagho EA. Acetylcholine as a possible neurotransmitter in penile erection.. J Urol 1989 Jun;141(6):1444-8.
          pubmed: 2566691doi: 10.1016/s0022-5347(17)41342-5google scholar: lookup
        32. Roy JB, Petrone RL, Said SI. A clinical trial of intracavernous vasoactive intestinal peptide to induce penile erection.. J Urol 1990 Feb;143(2):302-4.
          pubmed: 2405186doi: 10.1016/s0022-5347(17)39939-1google scholar: lookup
        33. Cocks TM, Angus JA. Comparison of relaxation responses of vascular and non-vascular smooth muscle to endothelium-derived relaxing factor (EDRF), acidified sodium nitrite (NO) and sodium nitroprusside.. Naunyn Schmiedebergs Arch Pharmacol 1990 Apr;341(4):364-72.
          pubmed: 2333103doi: 10.1007/BF00180663google scholar: lookup
        34. Tare M, Parkington HC, Coleman HA, Neild TO, Dusting GJ. Hyperpolarization and relaxation of arterial smooth muscle caused by nitric oxide derived from the endothelium.. Nature 1990 Jul 5;346(6279):69-71.
          pubmed: 2366864doi: 10.1038/346069a0google scholar: lookup
        35. Ignarro LJ, Bush PA, Buga GM, Wood KS, Fukuto JM, Rajfer J. Nitric oxide and cyclic GMP formation upon electrical field stimulation cause relaxation of corpus cavernosum smooth muscle.. Biochem Biophys Res Commun 1990 Jul 31;170(2):843-50.
          pubmed: 2166511doi: 10.1016/0006-291x(90)92168-ygoogle scholar: lookup
        36. Wolin MS, Cherry PD, Rodenburg JM, Messina EJ, Kaley G. Methylene blue inhibits vasodilation of skeletal muscle arterioles to acetylcholine and nitric oxide via the extracellular generation of superoxide anion.. J Pharmacol Exp Ther 1990 Sep;254(3):872-6.
          pubmed: 2168487
        37. Kim N, Azadzoi KM, Goldstein I, Saenz de Tejada I. A nitric oxide-like factor mediates nonadrenergic-noncholinergic neurogenic relaxation of penile corpus cavernosum smooth muscle.. J Clin Invest 1991 Jul;88(1):112-8.
          pubmed: 1647413doi: 10.1172/JCI115266google scholar: lookup
        38. Stief CG, Wetterauer U, Schaebsdau FH, Jonas U. Calcitonin-gene-related peptide: a possible role in human penile erection and its therapeutic application in impotent patients.. J Urol 1991 Oct;146(4):1010-4.
          pubmed: 1895414doi: 10.1016/s0022-5347(17)37989-2google scholar: lookup
        39. Holmquist F, Stief CG, Jonas U, Andersson KE. Effects of the nitric oxide synthase inhibitor NG-nitro-L-arginine on the erectile response to cavernous nerve stimulation in the rabbit.. Acta Physiol Scand 1991 Nov;143(3):299-304.
          pubmed: 1722938doi: 10.1111/j.1748-1716.1991.tb09236.xgoogle scholar: lookup
        40. Liu XR, Gillespie JS, Gibson IF, Martin W. Effects of NG-substituted analogues of L-arginine on NANC relaxation of the rat anococcygeus and bovine retractor penis muscles and the bovine penile artery.. Br J Pharmacol 1991 Sep;104(1):53-8.
          pubmed: 1786518doi: 10.1111/j.1476-5381.1991.tb12384.xgoogle scholar: lookup
        41. Pickard RS, Powell PH, Zar MA. The effect of inhibitors of nitric oxide biosynthesis and cyclic GMP formation on nerve-evoked relaxation of human cavernosal smooth muscle.. Br J Pharmacol 1991 Nov;104(3):755-9.
          pubmed: 1665750doi: 10.1111/j.1476-5381.1991.tb12500.xgoogle scholar: lookup
        42. Burnett AL, Lowenstein CJ, Bredt DS, Chang TS, Snyder SH. Nitric oxide: a physiologic mediator of penile erection.. Science 1992 Jul 17;257(5068):401-3.
          pubmed: 1378650doi: 10.1126/science.1378650google scholar: lookup
        43. Schmidt HH. NO., CO and .OH. Endogenous soluble guanylyl cyclase-activating factors.. FEBS Lett 1992 Jul 27;307(1):102-7.
          pubmed: 1353461doi: 10.1016/0014-5793(92)80910-9google scholar: lookup
        44. Holmquist F, Hedlund H, Andersson KE. Characterization of inhibitory neurotransmission in the isolated corpus cavernosum from rabbit and man.. J Physiol 1992 Apr;449:295-311.
          pubmed: 1326047doi: 10.1113/jphysiol.1992.sp019087google scholar: lookup
        45. Mayer B, Brunner F, Schmidt K. Inhibition of nitric oxide synthesis by methylene blue.. Biochem Pharmacol 1993 Jan 26;45(2):367-74.
          pubmed: 7679577doi: 10.1016/0006-2952(93)90072-5google scholar: lookup
        46. Trigo-Rocha F, Aronson WJ, Hohenfellner M, Ignarro LJ, Rajfer J, Lue TF. Nitric oxide and cGMP: mediators of pelvic nerve-stimulated erection in dogs.. Am J Physiol 1993 Feb;264(2 Pt 2):H419-22.
          pubmed: 8383456doi: 10.1152/ajpheart.1993.264.2.H419google scholar: lookup
        47. Ayajiki K, Okamura T, Toda N. Nitric oxide mediates, and acetylcholine modulates, neurally induced relaxation of bovine cerebral arteries.. Neuroscience 1993 Jun;54(3):819-25.
          pubmed: 8332264doi: 10.1016/0306-4522(93)90251-agoogle scholar: lookup

        Citations

        This article has been cited 11 times.
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          doi: 10.3389/fphar.2017.00660pubmed: 28993731google scholar: lookup
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          doi: 10.1002/cphy.c160011pubmed: 28333380google scholar: lookup
        3. Yetik-Anacak G, Sorrentino R, Linder AE, Murat N. Gas what: NO is not the only answer to sexual function. Br J Pharmacol 2015 Mar;172(6):1434-54.
          doi: 10.1111/bph.12700pubmed: 24661203google scholar: lookup
        4. González-Corrochano R, La Fuente J, Cuevas P, Fernández A, Chen M, Sáenz de Tejada I, Angulo J. Ca2+ -activated K+ channel (KCa) stimulation improves relaxant capacity of PDE5 inhibitors in human penile arteries and recovers the reduced efficacy of PDE5 inhibition in diabetic erectile dysfunction. Br J Pharmacol 2013 May;169(2):449-61.
          doi: 10.1111/bph.12143pubmed: 23441682google scholar: lookup
        5. Fernandes VS, Martínez-Sáenz A, Recio P, Ribeiro AS, Sánchez A, Martínez MP, Martínez AC, García-Sacristán A, Orensanz LM, Prieto D, Hernández M. Mechanisms involved in the nitric oxide-induced vasorelaxation in porcine prostatic small arteries. Naunyn Schmiedebergs Arch Pharmacol 2011 Sep;384(3):245-53.
          doi: 10.1007/s00210-011-0666-2pubmed: 21748357google scholar: lookup
        6. Dalsgaard T, Kroigaard C, Misfeldt M, Bek T, Simonsen U. Openers of small conductance calcium-activated potassium channels selectively enhance NO-mediated bradykinin vasodilatation in porcine retinal arterioles. Br J Pharmacol 2010 Jul;160(6):1496-508.
          doi: 10.1111/j.1476-5381.2010.00803.xpubmed: 20590639google scholar: lookup
        7. Kun A, Matchkov VV, Stankevicius E, Nardi A, Hughes AD, Kirkeby HJ, Demnitz J, Simonsen U. NS11021, a novel opener of large-conductance Ca(2+)-activated K(+) channels, enhances erectile responses in rats. Br J Pharmacol 2009 Nov;158(6):1465-76.
          doi: 10.1111/j.1476-5381.2009.00404.xpubmed: 19845682google scholar: lookup
        8. Waldkirch E, Uckert S, Yildirim H, Sohn M, Jonas U, Stief CG, Andersson KE, Hedlund P. Cyclic AMP-specific and cyclic GMP-specific phosphodiesterase isoenzymes in human cavernous arteries--immunohistochemical distribution and functional significance. World J Urol 2005 Dec;23(6):405-10.
          doi: 10.1007/s00345-005-0026-2pubmed: 16292559google scholar: lookup
        9. Briganti A, Salonia A, Deho' F, Zanni G, Barbieri L, Rigatti P, Montorsi F. Clinical update on phosphodiesterase type-5 inhibitors for erectile dysfunction. World J Urol 2005 Dec;23(6):374-84.
          doi: 10.1007/s00345-005-0022-6pubmed: 16273417google scholar: lookup
        10. Prieto D, Arcos LR, Martínez P, Benedito S, García-Sacristán A, Hernández M. Heterogeneity of the neuropeptide Y (NPY) contractile and relaxing receptors in horse penile small arteries. Br J Pharmacol 2004 Dec;143(8):976-86.
          doi: 10.1038/sj.bjp.0706005pubmed: 15557288google scholar: lookup
        11. Andersson KE, Stief CG. Neurotransmission and the contraction and relaxation of penile erectile tissues. World J Urol 1997;15(1):14-20.
          doi: 10.1007/BF01275151pubmed: 9066089google scholar: lookup
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