期刊
BRITISH JOURNAL OF PHARMACOLOGY
卷 169, 期 2, 页码 413-425出版社
WILEY
DOI: 10.1111/bph.12121
关键词
aorta; mesenteric resistance arteries; -adrenoceptor subtypes; cAMP; cGMP; mRNA
资金
- Ministerio de Economia y Competitividad [SAF2007-62120, SAF2010-19282]
- Fondo Europeo de Desarrollo Regional de la Union Europea (Fondo FEDER)
- Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias [FIS-PI070509]
- Generalitat de Catalunya [2009SGR-890]
- Ministerio de Educacion y Ciencia
Background and Purpose To analyse the relative contribution of 1-, 2- and 3-adrenoceptors (Adrb) to vasodilatation in conductance and resistance vessels, assessing the role of cAMP and/or NO/cGMP signalling pathways. Experimental Approach Rat mesenteric resistance artery (MRA) and aorta were used to analyse the Adrb expression by real-time-PCR and immunohistochemistry, and for the pharmacological characterization of Adrb-mediated activity by wire myography and tissue nucleotide accumulation. Key Results The mRNAs and protein for all Adrb were identified in endothelium and/or smooth muscle cells (SMCs) in both vessels. In MRA, Adrb1 signalled through cAMP, Adrb3 through both cAMP and cGMP, but Adrb2, did not activate nucleotide formation; isoprenaline relaxation was inhibited by propranolol (1, 2), CGP20712A (1), and SQ22536 (adenylyl cyclase inhibitor), but not by ICI118,551 (2), SR59230A (3), ODQ (soluble guanylyl cyclase inhibitor), L-NAME or endothelium removal. In aorta, Adrb1 signalled through cAMP, while 2- and 3-subtypes through cGMP; isoprenaline relaxation was inhibited by propranolol, ICI118,551, ODQ, L-NAME, and to a lesser extent, by endothelium removal. CL316243 (3-agonist) relaxed aorta, but not MRA. Conclusion and Implication Despite all three Adrb subtypes being found in both vessels, Adrb1, located in SMCs and acting through the adenylyl cyclase/cAMP pathway, are primarily responsible for vasodilatation in MRA. However, Adrb-mediated vasodilatation in aorta is driven by endothelial Adrb2 and Adrb3, but also by the Adrb2 present in SMCs, and is coupled to the NO/cGMP pathway. These results could help to understand the different physiological roles played by Adrb signalling in regulating conductance and resistance vessels.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据