Pharmacological properties of β-adrenoceptors mediating rat superior mesenteric artery relaxation and the effects of chemical sympathetic denervation

β-Adrenoceptors (β-ADRs) mediating the relaxation of rat superior mesenteric arteries (SMAs) were pharmacologically identified, and the effects of chemical sympathetic denervation on β-ADR-mediated relaxation were examined. The tension changes of endothelium-denuded SMAs were isometrically recorded...

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Veröffentlicht in:Life sciences (1973) 2020-01, Vol.241, p.117155, Article 117155
Hauptverfasser: Obara, Keisuke, Shigematsu, Mai, Takahasi, Hiromi, Iiboshi, Yuri, Yoshioka, Kento, Kasuya, Yoshitoshi, Tanaka, Yoshio
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Sprache:eng
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Zusammenfassung:β-Adrenoceptors (β-ADRs) mediating the relaxation of rat superior mesenteric arteries (SMAs) were pharmacologically identified, and the effects of chemical sympathetic denervation on β-ADR-mediated relaxation were examined. The tension changes of endothelium-denuded SMAs were isometrically recorded and the mRNA of endothelium-denuded SMA β-ADR was detected using RT-PCR. In endothelium-denuded SMAs contracted with ≥10−7 M phenylephrine (an α1-ADR agonist), isoprenaline (a β-ADR agonist)-induced relaxation was competitively inhibited by 3 × 10−9–10−8 M propranolol (a β1,2-ADR antagonist), but not further affected by ≥10−8 M propranolol. Although isoprenaline-induced relaxation was not affected by ICI-118,551 (10−9–10−8 M; a β2-ADR antagonist), it was competitively inhibited by atenolol (10−7–3 × 10−7 M; a β1-ADR antagonist) in the presence of ICI-118,551. In the presence of 10−7 M propranolol, isoprenaline- and CGP-12177A (a β3-ADR partial agonist)-induced relaxation was competitively inhibited by high concentrations of bupranolol (a β1,2,3-ADR antagonist), with pA2 values of 6.49 and 5.76, respectively. We detected the mRNA of β1- and β3-ADRs in endothelium-denuded SMAs. Treatment with 6-hydroxydopamine (a catecholaminergic neurotoxin) reduced maximal isoprenaline-induced relaxation in the presence and absence of 10−7 M propranolol, but not CGP-12177A-induced relaxation. Isoprenaline-induced relaxation of rat SMAs is mediated by β1- and β3-ADRs. β-ADR-mediated relaxation of rat SMAs is shown to be attenuated by chemical sympathetic denervation. The differences in the effects of bupranolol and chemical sympathetic denervation on the responses to isoprenaline and CGP-12177A in rat SMAs might be explained by the possible presence of multiple β3-ADRs with different pharmacological properties. [Display omitted] •Functional β-adrenoceptors were studied in rat superior mesenteric artery (SMA).•SMA relaxation by isoprenaline involved β1-, and β3-adrenoceptors (ADRs).•SMA relaxation by isoprenaline was attenuated by chemical sympathetic denervation.•SMA relaxation by CGP-12177A was not attenuated by chemical sympathetic denervation.•Multiple β3-ADRs with distinct pharmacological properties may be present in rat SMA.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2019.117155