Vasorelaxing effects of propranolol in rat aorta and mesenteric artery: A role for nitric oxide and calcium entry blockade

Fernanda Priviero, Cleber E. Teixeira, Haroldo Alfredo Flores Toque, Mário A. Claudino, R Clinton Webb, Gilberto De Nucci, Angelina Zanesco, Edson Antunes

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


1. Propranolol has been prescribed successfully to patients with cardiovascular diseases, but the exact mechanisms by which it reduces peripheral vascular resistance have been poorly investigated. 2. The present study was designed to investigate the relaxing effects of propranolol in the rat isolated aorta and mesenteric artery, focusing on the contribution of the nitric oxide (NO)-cGMP pathway and calcium entry blockade. Relaxation responses to propranolol were obtained in precontracted rat aortic and mesenteric artery rings. 3. dl-Propranolol (10-100 μmol/L) produced concentration-dependent relaxations in the aorta and mesenteric artery rings with intact endothelium. The isomers d- and l-propranolol produced relaxation responses that were equipotent to the racemic mixture. 4. Metoprolol (10-100 μmol/L) produced slight relaxations, whereas atenolol (10-100 μmol/L) had no relaxant activity. 5. The NO inhibitor NG-nitro-l-arginine methyl ester (100 μmol/L) and the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3- a]quinoxalin-1-one (1 μmol/L), as well as removal of the endothelium, significantly reduced the relaxation responses induced by the lower concentrations of propranolol without affecting maximal responses. In addition, dl-propranolol markedly increased cGMP levels in endothelium-intact preparations. 6. In Ca2+-free Krebs' solution, dl-propranolol (10-100 μmol/L) caused marked rightward shift in the concentration-response curves to CaCl2, with a decrease of maximal responses in tissues with either intact or denuded endothelium. Nifedipine (1 μmol/L) in combination with dl-propranolol virtually abolished the CaCl2-induced contractile responses. 7. The relaxation responses induced by dl-propranolol were significantly reduced in aortic and mesenteric rings precontracted with phorbol-12,13-dibutyrate (1 μmol/L). 8. In conclusion, dl-propranolol relaxes arterial smooth muscle by mechanisms involving activation of the NO-cGMP pathway and calcium influx blockade, independent of β-adrenoceptor blockade.

Original languageEnglish (US)
Pages (from-to)448-455
Number of pages8
JournalClinical and Experimental Pharmacology and Physiology
Issue number5-6
StatePublished - May 1 2006
Externally publishedYes


  • Blood vessels
  • Calcium blockade
  • Endothelium
  • Propranolol
  • Relaxation

ASJC Scopus subject areas

  • Physiology
  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)


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