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

Abstract：

AIMS: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. MAIN METHODS:The tension changes of endothelium-denuded SMAs were isometrically recorded and the mRNA of endothelium-denuded SMA β-ADR was detected using RT-PCR. KEY FINDINGS: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. SIGNIFICANCE: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.

journal_name

Life Sci

journal_title

Life sciences

authors

Obara K,Shigematsu M,Takahasi H,Iiboshi Y,Yoshioka K,Kasuya Y,Tanaka Y

doi

10.1016/j.lfs.2019.117155

subject

Has Abstract

pub_date

2020-01-15 00:00:00

pages

117155

eissn

0024-3205

issn

1879-0631

pii

S0024-3205(19)31083-5

journal_volume

241

pub_type

杂志文章

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