title: Vascular effects of long-term propranolol administration after chronic nitric oxide blockade.
abstract: Long-term propranolol treatment reduces arterial blood pressure in hypertensive individuals mainly by reducing peripheral vascular resistance, but mechanisms underlying their vasodilatory effect remain poorly investigated. This study aimed to investigate whether long-term propranolol administration ameliorates the impairment of relaxing responses of aorta and mesenteric artery from rats made hypertensive by chronic nitric oxide (NO) deficiency, and underlying mechanisms mediating this phenomenon. Male Wistar rats were treated with N(omega)-Nitro-L-arginine methyl ester (L-NAME; 20 mg/rat/day) for four weeks. DL-Propranolol (30 mg/rat/day) was given concomitantly to L-NAME in the drinking water. Treatment with L-NAME markedly increased blood pressure, an effect largely attenuated by DL-propranolol. In phenylephrine-precontracted aortic rings, the reduction of relaxing responses for acetylcholine (0.001-10 microM) in L-NAME group was not modified by DL-propranolol, whereas in mesenteric rings the impairment of acetylcholine-induced relaxation by L-NAME was significantly attenuated by DL-propranolol. In mesenteric rings precontracted with KCl (80 mM), DL-propranolol failed to attenuate the impairment of acetylcholine-induced relaxation by L-NAME. The contractile responses to extracellular CaCl2 (1-10 mM) were increased in L-NAME group, and co-treatment with DL-propranolol reduced this response in both preparations in most Ca2+ concentrations used. The NO2/NO3 plasma levels and superoxide dismutase (SOD) activity were reduced in L-NAME-treated rats, both of which were significantly prevented by DL-propranolol. In conclusion, propranolol-induced amplification of the relaxation to acetylcholine in mesenteric arteries from L-NAME-treated rats is sensitive to depolarization. Additional mechanisms involving blockade of Ca2+ entry in the vascular smooth muscle and increase in NO bioavailability contributes to beneficial effects of long-term propranolol treatment.
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, P.O. Box 6111, 13084-971, Campinas, São Paulo, Brazil.
authors.forename: Fernanda B M
authors.initials: FB
authors.lastname: Priviero
authors.forename: Cleber E
authors.initials: CE
authors.lastname: Teixeira
authors.forename: Mário A
authors.initials: MA
authors.lastname: Claudino
authors.forename: Gilberto
authors.initials: G
authors.lastname: De Nucci
authors.forename: Angelina
authors.initials: A
authors.lastname: Zanesco
authors.forename: Edson
authors.initials: E
authors.lastname: Antunes
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001011:Aorta / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology; D001685:Biological Factors / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors; D006973:Hypertension / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D005996:Nitroglycerin / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000097:blood; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000959:Antihypertensive Agents; D001685:Biological Factors; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D011433:Propranolol; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D005996:Nitroglycerin; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester