β1- and β12-adrenergic receptor antagonists block 6-nitrodopamine-induced contractions of the rat isolated epididymal vas deferens

Naunyn Schmiedebergs Arch Pharmacol. 2022 Oct;395(10):1257-1268. doi: 10.1007/s00210-022-02268-6. Epub 2022 Jul 8.

Abstract

6-Nitrodopamine (6-ND) is an endogenous modulator of the contractility in the rat isolated epididymal vas deferens (RIEVD) and considered to be the main peripheral mediator of the emission process. Use of selective and unselective β-adrenergic receptor antagonists has been associated with ejaculatory failure. Here, the effects of selective β1- and β12-adrenergic receptor antagonists on RIEVD contractions induced by 6-ND, dopamine, noradrenaline, adrenaline, and electric-field stimulation (EFS) were investigated. The selective β1-adrenergic receptor antagonists atenolol (0.1 and 1 µM), betaxolol (1 µM), and metoprolol (1 µM) and the unselective β12-adrenergic receptor antagonists propranolol (1 and 10 µM) and pindolol (10 µM) caused significant rightward shifts of the concentration-response curve to 6-ND (pA2 6.41, 6.91, 6.75, 6.47, and 5.74; for atenolol, betaxolol, metoprolol, propranolol, and pindolol), but had no effect on dopamine-, noradrenaline-, and adrenaline-induced contractions. The effects of selective β1- and β12-adrenergic receptor antagonists at a higher concentration (atenolol 1 µM, betaxolol 1 µM, metoprolol 1 µM, propranolol 10 µM, and pindolol 10 µM) also reduced the EFS-induced RIEVD contractions in control, but not in RIEVD obtained from L-NAME-treated animals. The selective β1-adrenoceptor agonist RO-363, the selective β2-adrenoceptor agonist salbutamol, and the selective β3-adrenoceptor agonist mirabegron, up to 300 µM, had no effect on the RIEVD tone. The results demonstrate that β1- and β1-/β2-adrenoceptor receptor antagonists act as 6-ND receptor antagonists in RIEVD, further confirming the main role of 6-ND in the RIEVD contractility.

Keywords: EFS; Ejaculation disorder; L-NAME; Nitrocatecholamines.

MeSH terms

  • Adrenergic beta-1 Receptor Antagonists / pharmacology
  • Adrenergic beta-2 Receptor Antagonists / pharmacology
  • Adrenergic beta-Agonists / pharmacology
  • Adrenergic beta-Antagonists / pharmacology
  • Animals
  • Atenolol / pharmacology
  • Betaxolol / pharmacology
  • Dopamine / analogs & derivatives
  • Epinephrine / pharmacology
  • Male
  • Metoprolol / pharmacology
  • Norepinephrine / pharmacology
  • Pindolol / pharmacology
  • Propranolol* / pharmacology
  • Rats
  • Vas Deferens*

Substances

  • 6-nitrodopamine
  • Adrenergic beta-1 Receptor Antagonists
  • Adrenergic beta-2 Receptor Antagonists
  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Atenolol
  • Propranolol
  • Pindolol
  • Metoprolol
  • Betaxolol
  • Dopamine
  • Norepinephrine
  • Epinephrine