Tags

Type your tag names separated by a space and hit enter

Vasorelaxing effects of propranolol in rat aorta and mesenteric artery: a role for nitric oxide and calcium entry blockade.
Clin Exp Pharmacol Physiol. 2006 May-Jun; 33(5-6):448-55.CE

Abstract

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 micromol/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 micromol/L) produced slight relaxations, whereas atenolol (10-100 micromol/L) had no relaxant activity. 5. The NO inhibitor N(G)-nitro-L-arginine methyl ester (100 micromol/L) and the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (1 micromol/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 Ca(2+)-free Krebs' solution, DL-propranolol (10-100 micromol/L) caused marked rightward shift in the concentration-response curves to CaCl(2), with a decrease of maximal responses in tissues with either intact or denuded endothelium. Nifedipine (1 micromol/L) in combination with DL-propranolol virtually abolished the CaCl(2)-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 micromol/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 beta-adrenoceptor blockade.

Authors+Show Affiliations

Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16700877

Citation

Priviero, Fernanda B M., et al. "Vasorelaxing Effects of Propranolol in Rat Aorta and Mesenteric Artery: a Role for Nitric Oxide and Calcium Entry Blockade." Clinical and Experimental Pharmacology & Physiology, vol. 33, no. 5-6, 2006, pp. 448-55.
Priviero FB, Teixeira CE, Toque HA, et al. Vasorelaxing effects of propranolol in rat aorta and mesenteric artery: a role for nitric oxide and calcium entry blockade. Clin Exp Pharmacol Physiol. 2006;33(5-6):448-55.
Priviero, F. B., Teixeira, C. E., Toque, H. A., Claudino, M. A., Webb, R. C., De Nucci, G., Zanesco, A., & Antunes, E. (2006). Vasorelaxing effects of propranolol in rat aorta and mesenteric artery: a role for nitric oxide and calcium entry blockade. Clinical and Experimental Pharmacology & Physiology, 33(5-6), 448-55.
Priviero FB, et al. Vasorelaxing Effects of Propranolol in Rat Aorta and Mesenteric Artery: a Role for Nitric Oxide and Calcium Entry Blockade. Clin Exp Pharmacol Physiol. 2006 May-Jun;33(5-6):448-55. PubMed PMID: 16700877.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vasorelaxing effects of propranolol in rat aorta and mesenteric artery: a role for nitric oxide and calcium entry blockade. AU - Priviero,Fernanda B M, AU - Teixeira,Cleber E, AU - Toque,Haroldo A F, AU - Claudino,Mário A, AU - Webb,R Clinton, AU - De Nucci,Gilberto, AU - Zanesco,Angelina, AU - Antunes,Edson, PY - 2006/5/17/pubmed PY - 2007/8/9/medline PY - 2006/5/17/entrez SP - 448 EP - 55 JF - Clinical and experimental pharmacology & physiology JO - Clin Exp Pharmacol Physiol VL - 33 IS - 5-6 N2 - 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 micromol/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 micromol/L) produced slight relaxations, whereas atenolol (10-100 micromol/L) had no relaxant activity. 5. The NO inhibitor N(G)-nitro-L-arginine methyl ester (100 micromol/L) and the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (1 micromol/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 Ca(2+)-free Krebs' solution, DL-propranolol (10-100 micromol/L) caused marked rightward shift in the concentration-response curves to CaCl(2), with a decrease of maximal responses in tissues with either intact or denuded endothelium. Nifedipine (1 micromol/L) in combination with DL-propranolol virtually abolished the CaCl(2)-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 micromol/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 beta-adrenoceptor blockade. SN - 0305-1870 UR - https://www.unboundmedicine.com/medline/citation/16700877/Vasorelaxing_effects_of_propranolol_in_rat_aorta_and_mesenteric_artery:_a_role_for_nitric_oxide_and_calcium_entry_blockade_ L2 - https://doi.org/10.1111/j.1440-1681.2006.04386.x DB - PRIME DP - Unbound Medicine ER -