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Effect of clenbuterol on non-endothelial nitric oxide release in rat mesenteric arteries and the involvement of beta-adrenoceptors.
Br J Pharmacol. 1998 Jun; 124(3):473-8.BJ

Abstract

1. The aim of the present study was to explore the contribution of adrenergic, sensory and nitrergic innervations to the inhibitory effects of the beta2-adrenoceptor agonist clenbuterol on responses to electrical field stimulation (EFS, 200 mA, 0.3 ms, 1-16 Hz, for 30 s, at 1 min interval) in rat mesenteric artery segments without endothelium and the possible involvement of adrenergic, sensory and nitrergic innervations. 2. Clenbuterol (1 microM) reduced EFS-induced contractile responses, and this effect was reversed by the beta-antagonist propranolol (1 microM) (contraction at 16 Hz expressed as % of 75 mM K+-induced contraction was: control, 69+/-9, clenbuterol, 31+/-6, n=13, P<0.001; control, 83+/-5, clenbuterol+propranolol 70+/-7, n=11, P>0.05). 3. In arteries preincubated with [3H]-noradrenaline (NA), clenbuterol did not modify the tritium overflow evoked by EFS (200 mA, 0.3 ms, 4 Hz, for 60 s; ratio between tritium release in the second and first stimuli was: control, 0.80+/-0.05 and clenbuterol added before second stimulus, 0.91+/-0.11, n=5, P>0.05). 4. The nitric oxide (NO) synthase inhibitors NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine methyl ester (L-NAME) (10 and 100 microM), and the guanylate cyclase inhibitor methylene blue (10 microM) increased the contractions caused by EFS (% contraction at 16 Hz, control, 81+/-7, n=26; 10 microM L-NMMA, 109+/-12, n=8, P<0.05; methylene blue, 119+/-6, n=6, P<0.05). However, these contractions were decreased by the NO synthase substrate L-arginine 10 microM (14+/-6%, n=6, P<0.001), but not modified by either the sensory neurones toxin capsaicin (0.5 microM, 75+/-6%, n=6, P>0.05) or the protein synthesis inhibitor cycloheximide (10 microM, 83+/-6%, n=8, P>0.05). None of these drugs altered the concentration-response curves to exogenous NA (n=7). 5. Pretreatment with capsaicin or cycloheximide did not modify the reduction of the EFS-evoked contraction provoked by clenbuterol. However the presence of L-NMMA (or L-NAME) or methylene blue did decrease the effect of clenbuterol (% contraction at 16 Hz, clenbuterol, 31+/-6, n=13; clenbuterol+10 microM L-NMMA, 93+/-11, n=8, P<0.05; clenbuterol+methylene blue, 90+/-7, n=6, P<0.05). 6. These results suggest that the reduction caused by clenbuterol in the contraction induced by EFS in rat mesenteric arteries seems to be mediated by NO release, through the activation of beta2-adrenoceptors probably present on nitrergic nerves.

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Authors+Show Affiliations

Marín J
Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, Madrid, Spain.
Balfagón G
No affiliation info available

MeSH

Adrenergic beta-AgonistsAnimalsClenbuterolElectric StimulationEnzyme InhibitorsGuanylate CyclaseIn Vitro TechniquesMaleMembrane PotentialsMesenteric ArteriesMuscle ContractionMuscle, Smooth, VascularNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IINorepinephrineProtein Synthesis InhibitorsRatsRats, WistarReceptors, Adrenergic, beta

Pub Type(s)

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

Language

eng

PubMed ID

9647470

Citation

Marín, J, and G Balfagón. "Effect of Clenbuterol On Non-endothelial Nitric Oxide Release in Rat Mesenteric Arteries and the Involvement of Beta-adrenoceptors." British Journal of Pharmacology, vol. 124, no. 3, 1998, pp. 473-8.
Marín J, Balfagón G. Effect of clenbuterol on non-endothelial nitric oxide release in rat mesenteric arteries and the involvement of beta-adrenoceptors. Br J Pharmacol. 1998;124(3):473-8.
Marín, J., & Balfagón, G. (1998). Effect of clenbuterol on non-endothelial nitric oxide release in rat mesenteric arteries and the involvement of beta-adrenoceptors. British Journal of Pharmacology, 124(3), 473-8.
Marín J, Balfagón G. Effect of Clenbuterol On Non-endothelial Nitric Oxide Release in Rat Mesenteric Arteries and the Involvement of Beta-adrenoceptors. Br J Pharmacol. 1998;124(3):473-8. PubMed PMID: 9647470.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of clenbuterol on non-endothelial nitric oxide release in rat mesenteric arteries and the involvement of beta-adrenoceptors. AU - Marín,J, AU - Balfagón,G, PY - 1998/7/1/pubmed PY - 1998/7/1/medline PY - 1998/7/1/entrez SP - 473 EP - 8 JF - British journal of pharmacology JO - Br J Pharmacol VL - 124 IS - 3 N2 - 1. The aim of the present study was to explore the contribution of adrenergic, sensory and nitrergic innervations to the inhibitory effects of the beta2-adrenoceptor agonist clenbuterol on responses to electrical field stimulation (EFS, 200 mA, 0.3 ms, 1-16 Hz, for 30 s, at 1 min interval) in rat mesenteric artery segments without endothelium and the possible involvement of adrenergic, sensory and nitrergic innervations. 2. Clenbuterol (1 microM) reduced EFS-induced contractile responses, and this effect was reversed by the beta-antagonist propranolol (1 microM) (contraction at 16 Hz expressed as % of 75 mM K+-induced contraction was: control, 69+/-9, clenbuterol, 31+/-6, n=13, P<0.001; control, 83+/-5, clenbuterol+propranolol 70+/-7, n=11, P>0.05). 3. In arteries preincubated with [3H]-noradrenaline (NA), clenbuterol did not modify the tritium overflow evoked by EFS (200 mA, 0.3 ms, 4 Hz, for 60 s; ratio between tritium release in the second and first stimuli was: control, 0.80+/-0.05 and clenbuterol added before second stimulus, 0.91+/-0.11, n=5, P>0.05). 4. The nitric oxide (NO) synthase inhibitors NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine methyl ester (L-NAME) (10 and 100 microM), and the guanylate cyclase inhibitor methylene blue (10 microM) increased the contractions caused by EFS (% contraction at 16 Hz, control, 81+/-7, n=26; 10 microM L-NMMA, 109+/-12, n=8, P<0.05; methylene blue, 119+/-6, n=6, P<0.05). However, these contractions were decreased by the NO synthase substrate L-arginine 10 microM (14+/-6%, n=6, P<0.001), but not modified by either the sensory neurones toxin capsaicin (0.5 microM, 75+/-6%, n=6, P>0.05) or the protein synthesis inhibitor cycloheximide (10 microM, 83+/-6%, n=8, P>0.05). None of these drugs altered the concentration-response curves to exogenous NA (n=7). 5. Pretreatment with capsaicin or cycloheximide did not modify the reduction of the EFS-evoked contraction provoked by clenbuterol. However the presence of L-NMMA (or L-NAME) or methylene blue did decrease the effect of clenbuterol (% contraction at 16 Hz, clenbuterol, 31+/-6, n=13; clenbuterol+10 microM L-NMMA, 93+/-11, n=8, P<0.05; clenbuterol+methylene blue, 90+/-7, n=6, P<0.05). 6. These results suggest that the reduction caused by clenbuterol in the contraction induced by EFS in rat mesenteric arteries seems to be mediated by NO release, through the activation of beta2-adrenoceptors probably present on nitrergic nerves. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/9647470/Effect_of_clenbuterol_on_non_endothelial_nitric_oxide_release_in_rat_mesenteric_arteries_and_the_involvement_of_beta_adrenoceptors_ L2 - https://doi.org/10.1038/sj.bjp.0701856 DB - PRIME DP - Unbound Medicine ER -