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Home / Equine Research Bank / Br J Pharmacol / Involvement of nitric oxide in the non-adrenergic non-cholin...
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

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        Citations

        This article has been cited 11 times.
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