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VASORELAXING EFFECTS OF PROPRANOLOL IN RAT AORTA AND MESENTERIC ARTERY: A ROLE FOR NITRIC OXIDE AND CALCIUM ENTRY BLOCKADE
Author(s) -
Priviero Fernanda BM,
Teixeira Cleber E,
Toque Haroldo AF,
Claudino Mário A,
Webb R Clinton,
De Nucci Gilberto,
Zanesco Angelina,
Antunes Edson
Publication year - 2006
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2006.04386.x
Subject(s) - propranolol , aorta , nifedipine , chemistry , nitric oxide , endocrinology , medicine , atenolol , mesenteric arteries , calcium , endothelium , pharmacology , artery , blood pressure
SUMMARY1 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 mmol/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 mmol/L) produced slight relaxations, whereas atenolol (10–100 mmol/L) had no relaxant activity. 5 The NO inhibitor N G ‐nitro‐ l ‐arginine methyl ester (100 mmol/L) and the soluble guanylate cyclase inhibitor 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (1 mmol/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 mmol/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 mmol/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 mmol/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 b‐adrenoceptor blockade.