Prejunctional alpha 2-adrenoceptors inhibit nitrergic neurotransmission in horse penile resistance arteries.
Abstract: To study the influence of alpha-adrenergic stimuli on non-adrenergic non-cholinergic (NANC) neurogenic relaxation in isolated horse penile resistance arteries. Methods: Deep intracavernous penile arteries with an internal lumen diameter of 200-500 microns., isolated from the corpus cavernosum of young horses, were mounted in microvascular myographs for isometric tension recording and electrical field stimulation (EFS) of autonomic nerve terminals. Results: In the presence of guanethidine (10(-5) M) and atropine (10(-7) M) tone of the arteries was raised by the thromboxane analogue, U46619. EFS (1, 4 and 32 Hz) induced frequency-dependent relaxations, which were abolished in the presence of tetrodotoxin, while NG-nitro-L-arginine (L-NOARG, 10(-4) M) abolished the relaxations to EFS at 1 Hz, and significantly reduced the relaxations at 4 Hz and 32 Hz by 82.5 +/- 10.2% and 52.9 +/- 4.7%, respectively (n = 6). EFS induced relaxations of a similar magnitude in penile arteries contracted with U46619 or the alpha 1-adrenoceptor agonist, phenylephrine, while the alpha 2-adrenoceptor agonist, BHT920 (10(-6) M), produced an inhibitory effect on the EFS-evoked relaxations which was inversely related to the stimulus frequency (1, 4 and 32 Hz). BHT920 had no effect on the relaxations induced by exogenous nitric oxide (NO), added as acidified sodium nitrite (10(-6)-10(-3) M). The inhibitory effect of BHT920 on NANC relaxations was reversed by 10(-7) M rauwolscine. Conclusions: These results suggest that the release of a NANC neurotransmitter primarily thought to be NO is inhibited by stimulation of prejunctional alpha 2-adrenoceptors in horse penile resistance arteries.
Publication Date: 1997-06-01 PubMed ID: 9146670
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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The research investigates how alpha-adrenergic stimuli impact the non-adrenergic non-cholinergic (NANC) neurogenic relaxation in isolated horse penile resistance arteries, concluding that the alpha 2-adrenoceptor stimulation inhibits the release of NANC neurotransmitters, primarily understood to be Nitric oxide (NO).
Objective and Methods
- The researchers in this study wanted to understand how alpha-adrenergic stimuli impact the non-adrenergic non-cholinergic (NANC) neurogenic relaxation of horse penile resistance arteries.
- To study this effect, they isolated deep intracavernous penile arteries from young horses’ corpus cavernosum and mounted them in microvascular myographs for isometric tension recording and electrical field stimulation (EFS) of autonomic nerve terminals.
Results and Findings
- In their experiments, they raised the artery tone using a thromboxane analogue, U46619, in the presence of guanethidine and atropine. EFS induced frequency-dependent relaxations of the arteries.
- The artery relaxations induced by EFS were abolished in the presence of tetrodotoxin, and reduced significantly (up to 82.5%) by NG-nitro-L-arginine (L-NOARG).
- A similar relaxation magnitude induced by EFS was observed in penile arteries contracted with U46619 or the alpha 1-adrenoceptor agonist, phenylephrine.
- However, the alpha 2-adrenoceptor agonist, BHT920, inhibited the EFS-evoked relaxations, an effect that was inversely related to the stimulus frequency.
- This inhibitory effect of BHT920 on NANC relaxations had no impact on the relaxations induced by exogenously added NO, but was reversed by rauwolscine.
Conclusions
- The study concludes that prejunctional alpha 2-adrenoceptors inhibit the release of a NANC neurotransmitter, primarily believed to be NO, in horse penile resistance arteries.
- This finding is critical to understanding the physiological and pharmacological activities of these arteries, and it suggests potential treatment targets for diseases relating to erectile dysfunction.
Cite This Article
APA
Simonsen U, Prieto D, Hernández M, Sáenz de Tejada I, García-Sacristán A.
(1997).
Prejunctional alpha 2-adrenoceptors inhibit nitrergic neurotransmission in horse penile resistance arteries.
J Urol, 157(6), 2356-2360.
Publication
Researcher Affiliations
- Departamento de Fisiología, Facultad de Veterinaria, Universidad Complutense de Madrid, Spain.
MeSH Terms
- 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
- Adrenergic alpha-Agonists / pharmacology
- Animals
- Arteries / drug effects
- Arteries / physiology
- Azepines / pharmacology
- Electric Stimulation
- Enzyme Inhibitors / pharmacology
- Horses
- Male
- Muscle Relaxation / drug effects
- Muscle, Smooth, Vascular / drug effects
- Nitric Oxide / physiology
- Nitroarginine / pharmacology
- Penis / blood supply
- Penis / drug effects
- Prostaglandin Endoperoxides, Synthetic / pharmacology
- Receptors, Adrenergic, alpha-2 / drug effects
- Receptors, Adrenergic, alpha-2 / physiology
- Thromboxane A2 / analogs & derivatives
- Thromboxane A2 / pharmacology
- Vasoconstrictor Agents / pharmacology
Grant Funding
- DK-40487 / NIDDK NIH HHS
- R01-DK-39080 / NIDDK NIH HHS
Citations
This article has been cited 7 times.- Adam DR, Alem MM. Erectile Dysfunction: Pharmacological Pathways with Understudied Potentials. Biomedicines 2022 Dec 25;11(1).
- Jabir NR, Firoz CK, Zughaibi TA, Alsaadi MA, Abuzenadah AM, Al-Asmari AI, Alsaieedi A, Ahmed BA, Ramu AK, Tabrez S. A literature perspective on the pharmacological applications of yohimbine. Ann Med 2022 Dec;54(1):2861-2875.
- Lee JK, Tan RB, Chung E. Erectile dysfunction treatment and traditional medicine-can East and West medicine coexist?. Transl Androl Urol 2017 Feb;6(1):91-100.
- Corazza O, Martinotti G, Santacroce R, Chillemi E, Di Giannantonio M, Schifano F, Cellek S. Sexual enhancement products for sale online: raising awareness of the psychoactive effects of yohimbine, maca, horny goat weed, and Ginkgo biloba. Biomed Res Int 2014;2014:841798.
- Ho CC, Tan HM. Rise of herbal and traditional medicine in erectile dysfunction management. Curr Urol Rep 2011 Dec;12(6):470-8.
- Recio P, Orensanz LM, Martínez MP, Navarro-Dorado J, Bustamante S, García-Sacristán A, Prieto D, Hernández M. Noradrenergic vasoconstriction of pig prostatic small arteries. Naunyn Schmiedebergs Arch Pharmacol 2008 Feb;376(6):397-406.
- Mizusawa H, Hedlund P, Sjunnesson J, Brioni JD, Sullivan JP, Andersson KE. Enhancement of apomorphine-induced penile erection in the rat by a selective alpha(1D)-adrenoceptor antagonist. Br J Pharmacol 2002 Jul;136(5):701-8.
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