Vascular effects of long-term propranolol administration after chronic nitric oxide blockade

Fernanda Priviero, Cleber E. Teixeira, Mário A. Claudino, Gilberto D. Nucci, Angelina Zanesco, Edson Antunes

Research output: Contribution to journalArticle

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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 Nω-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 μM) 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.

Original languageEnglish (US)
Pages (from-to)189-196
Number of pages8
JournalEuropean Journal of Pharmacology
Volume571
Issue number2-3
DOIs
StatePublished - Oct 1 2007
Externally publishedYes

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Propranolol
Blood Vessels
Nitric Oxide
Acetylcholine
Mesenteric Arteries
Vascular Resistance
Phenylephrine
Vascular Smooth Muscle
Drinking Water
Biological Availability
Superoxide Dismutase
Aorta
Wistar Rats
Arterial Pressure
Blood Pressure

Keywords

  • Arterial reactivity
  • Endothelial dysfunction
  • Endothelium-derived hyperpolarizing factor
  • Nitric oxide bioavailability
  • β-adrenoceptor antagonist

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Vascular effects of long-term propranolol administration after chronic nitric oxide blockade. / Priviero, Fernanda; Teixeira, Cleber E.; Claudino, Mário A.; Nucci, Gilberto D.; Zanesco, Angelina; Antunes, Edson.

In: European Journal of Pharmacology, Vol. 571, No. 2-3, 01.10.2007, p. 189-196.

Research output: Contribution to journalArticle

Priviero, Fernanda ; Teixeira, Cleber E. ; Claudino, Mário A. ; Nucci, Gilberto D. ; Zanesco, Angelina ; Antunes, Edson. / Vascular effects of long-term propranolol administration after chronic nitric oxide blockade. In: European Journal of Pharmacology. 2007 ; Vol. 571, No. 2-3. pp. 189-196.
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AU - Claudino, Mário A.

AU - Nucci, Gilberto D.

AU - Zanesco, Angelina

AU - Antunes, Edson

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AB - 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 Nω-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 μM) 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.

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