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Life sciences2000; 67(11); 1355-1368; doi: 10.1016/s0024-3205(00)00724-4

Evidence of histamine receptor function in isolated horse penile dorsal arteries.

Abstract: The effect of histamine (10(-9)-10(-3) M) on horse penile dorsal artery was evaluated. Precontracted vessels showed a biphasic response (relaxation-contraction) to histamine, while at basal tone, histamine only induced a contractile effect. The H1 receptor agonist, 2-pyridylethylamine (PEA) (10(-9)-10(-3) M), induced concentration-dependent relaxation in precontracted rings and provoked vasoconstriction at basal tone. Mepyramine (10(-9)-10(8) M), an H1 receptor antagonist, competitively antagonized the relaxant response to histamine (pA2 = 9.7) and PEA (pA2 = 9.2). At basal tone, mepyramine (10(-10)-10(-8) M) also caused a rightward shift in the histamine contraction curve (pA2 = 10.1). Mepyramine (10(-9)-10(-8) M)/PEA Schild plots for resting vessels yielded a pA2 value of 9.4. A regulatory role for H2 and H3 receptors was precluded since there was no response to their agonists (dimaprit (10(-9)-10(-3) M), (R)-alpha-methylhistamine (10(-10)- 3 x 10(-4) M)), and antagonists (cimetidine (10(-5) M), thioperamide (10(-6) M)) did not affect control curves. Removal of the endothelium abolished the relaxant component causing a leftward shift in the contractile component in precontracted rings, with no effect on maximum contraction. Inhibitors of nitric oxide (NO) synthesis, L-NAME (3 x 10(-4) M) and L-NOARG (3 x 10(-4) M), modified the relaxant response while contraction was unaffected. L-Arginine (3 x 10(-4) M) potentiated maximum relaxation but did not affect contraction in precontracted rings. Effects of a prostanoid and K+ channels were ruled out. The biphasic response of precontracted vessels persisted in the presence of indomethacin (3 x 10(-6) M), tetraethylammonium (10(-3) M) and gliblenclamide (10(-5) M). L-NAME plus indomethacin, or this combination plus TEA or glibenclamide produced similar effects as isolated treatments. In resting vessels, histamine contraction was also unaffected by the lack of endothelium, or L-NAME, L-arginine or indomethacin pretreatment. The biphasic response to histamine is probably mediated by H1 receptors with a partial role for NO in the relaxant response in precontracted vessels. In the absence of tone, the contractile effect may be mediated by direct action on smooth muscle.
Publication Date: 2000-09-06 PubMed ID: 10972204DOI: 10.1016/s0024-3205(00)00724-4Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research investigates how histamine, acting on a specific type of receptor known as H1, influences the behavior of horse penile dorsal arteries. The study demonstrates that these arteries show a biphasic (two-phase) response to histamine – an initial relaxation followed by contraction. Importantly, it appears that this effect is mediated largely by H1 receptors, with nitric oxide also playing a partial role in promoting relaxation of precontracted vessels.

Study Design and Methods

  • The researchers treated isolated horse penile dorsal arteries with various concentrations of histamine and observed the resulting responses, including both relaxation and contraction.
  • They examined the role of H1 receptors in these responses, using PEA, an H1 receptor agonist (enhances the receptor’s action), and mepyramine, an H1 receptor antagonist (inhibits the receptor’s action).
  • To understand the involvement of other components in the response, experiments with nitric oxide inhibitors, and different receptor agonists (dimaprit, (R)-alpha-methylhistamine) and antagonists (cimetidine, thioperamide) were also conducted.
  • Endothelium (the inner lining of the blood vessels) was also removed in some experiments to see its effect on the histamine-induced responses.

Key Findings

  • Histamine induced a two-part response: initial relaxation followed by contraction in precontracted vessels, but only a contractile effect in vessels at their baseline tone.
  • The H1 receptor agonist PEA reproduced this response pattern, suggesting a key role for H1 receptors.
  • The H1 receptor antagonist mepyramine blocked the relaxing effect of histamine, supporting the importance of H1 receptors in mediating this response.
  • Researchers found no evidence for a role of H2 and H3 receptors as there was no response to their respective agonists and antagonists.
  • The removal of the endothelium or nitric oxide synthesis inhibitors altered the relaxant response but did not affect the maximal contraction induced by histamine.

Conclusion and Implications

  • The study concluded that the two-part response to histamine in horse penile dorsal arteries is most likely mediated by H1 receptors, with some involvement of nitric oxide in promoting relaxation.
  • The findings could provide valuable insights into the mechanisms by which histamine influences blood vessels’ behavior and possibly contribute to understanding of diseases involving abnormal vasoreactivity.

Cite This Article

APA
Martínez AC, Rivera L, Raposo R, García-Sacristán A, Benedito S. (2000). Evidence of histamine receptor function in isolated horse penile dorsal arteries. Life Sci, 67(11), 1355-1368. https://doi.org/10.1016/s0024-3205(00)00724-4

Publication

ISSN: 0024-3205
NlmUniqueID: 0375521
Country: Netherlands
Language: English
Volume: 67
Issue: 11
Pages: 1355-1368

Researcher Affiliations

Martínez, A C
  • Sección Departamental de Fisiología Animal, Facultad de Farmacia, Universidad Complutense, Madrid, Spain.
Rivera, L
    Raposo, R
      García-Sacristán, A
        Benedito, S

          MeSH Terms

          • Animals
          • Arteries / drug effects
          • Arteries / metabolism
          • Endothelium, Vascular / drug effects
          • Endothelium, Vascular / metabolism
          • Histamine / pharmacology
          • Histamine Agonists / pharmacology
          • Horses
          • In Vitro Techniques
          • Male
          • Penis / blood supply
          • Receptors, Histamine / metabolism

          Citations

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