期刊
CIRCULATION
卷 107, 期 21, 页码 2747-2752出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.CIR.0000066912.58385.DE
关键词
nitric oxide; endothelium; receptors, adrenergic, beta
资金
- NHLBI NIH HHS [HL-55397] Funding Source: Medline
Background - Nebivolol and carvedilol are third-generation beta-adrenoreceptor antagonists, which unlike classic beta-blockers, have additional endothelium-dependent vasodilating properties specifically related to microcirculation by a molecular mechanism that still remains unclear. We hypothesized that nebivolol and carvedilol stimulate NO release from microvascular endothelial cells by extracellular ATP, which is a well-established potent autocrine and paracrine signaling factor modulating a variety of cellular functions through the activation of P2-purinoceptors. Methods and Results - Contraction and relaxation of renal glomerular vasculature were measured by determination of intracapillary volume with [H-3]-inulin. Biologically active NO was measured with highly sensitive porphyrinic NO microsensors in a single glomerular endothelial cell (GEC). Extracellular ATP was measured by a luciferin-luciferase assay. Enzymatic degradation of extracellular ATP by apyrase and blockade of P2Y-purinoceptors by suramin or reactive blue 2 inhibited both beta-blocker-induced glomerular vasorelaxations and beta-blocker-stimulated NO release from GECs. Both beta-blocker-induced vasorelaxations were in the micromolar concentration range identical to that required for the beta-blocker stimulation of ATP and NO release from GECs. The maximum of NO release for nebivolol and carvedilol was very similar (188 +/- 14 and 226 +/- 17, respectively). Blockade of ATP release by a mechanosensitive ion channel blocker, Gd3+, inhibited the beta-blocker - dependent release of ATP and NO from GECs. Conclusions - These results demonstrate for the first time that nebivolol and carvedilol induce relaxation of renal glomerular microvasculature through ATP efflux with consequent stimulation of P2Y-purinoceptor - mediated NO release from GECs.
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