Aldosterone mediates many of the physiological and pathophysiological/cardio-toxic effects of angiotensin II(Ang II). Its synthesis and secretion from the zona glomerulosa cells of the adrenal cortex, elevated in chro...Aldosterone mediates many of the physiological and pathophysiological/cardio-toxic effects of angiotensin II(Ang II). Its synthesis and secretion from the zona glomerulosa cells of the adrenal cortex, elevated in chronic heart failure(HF), is induced by Ang II type 1 receptors(AT1Rs). The AT1R is a G protein-coupled receptor, mainly coupling to Gq/11 proteins. However, it can also signal through β-arrestin-1(βarr1) or-2(βarr2), both of which mediate G protein-independent signaling. Over the past decade, a second, Gq/11 proteinindependent but βarr1-dependent signaling pathway emanating from the adrenocortical AT1R and leading to aldosterone production has become appreciated. Thus, it became apparent that AT1R antagonists that block both pathways equally well are warranted for fully effective aldosterone suppression in HF. This spurred the comparison of all of the currently marketed angiotensin receptor blockers(ARBs, AT1R antagonists or sartans) at blocking activation of the two signaling modes(G protein-, and βarr1-dependent) at the Ang IIactivated AT1R and hence, at suppression of aldosterone in vitro and in vivo. Although all agents are very potent inhibitors of G protein activation at the AT1R, candesartan and valsartan were uncovered to be the most potent ARBs at blocking βarr activation by Ang II and at suppressing aldosterone in vitro and in vivo in post-myocardial infarction HF animals. In contrast, irbesartan and losartan are virtually G protein-"biased" blockers at the human AT1R, with very low efficacy for βarr inhibition and aldosterone suppression. Therefore, candesartan and valsartan(and other, structurally similar compounds) may be the most preferred ARB agents for HF pharmacotherapy, as well as for treatment of other conditions characterized by elevated aldosterone.展开更多
目的评估螺内酯对胰岛素以及糖代谢的影响。方法通过检索PubMed、Web of Science、Embase、ClinicalTrials数据库,收集截至2016年3月的相关文献,纳入探究螺内酯对胰岛素敏感性或血糖影响的随机对照试验。结果共有20项随机平行对照以及...目的评估螺内酯对胰岛素以及糖代谢的影响。方法通过检索PubMed、Web of Science、Embase、ClinicalTrials数据库,收集截至2016年3月的相关文献,纳入探究螺内酯对胰岛素敏感性或血糖影响的随机对照试验。结果共有20项随机平行对照以及随机交叉对照试验被纳入。Meta分析结果显示:螺内酯不影响空腹血糖水平[标准化均数差(SMD)为-0.03(95%CI:-0.18~0.12)]、空腹胰岛素水平[SMD为-0.04(95%CI:-0.24~0.16)]或胰岛素抵抗指数[SMD为-0.09(95%CI:-0.24~0.06)],随机平行对照试验合并的糖化血红蛋白SMD为0.03(95%CI:-0.23~0.28)。结论螺内酯对空腹血糖、空腹胰岛素、胰岛素抵抗指数以及糖化血红蛋白均无明显影响。有糖代谢紊乱风险的患者使用螺内酯相对安全,并不会进一步加重糖代谢紊乱或胰岛素抵抗。展开更多
文摘Aldosterone mediates many of the physiological and pathophysiological/cardio-toxic effects of angiotensin II(Ang II). Its synthesis and secretion from the zona glomerulosa cells of the adrenal cortex, elevated in chronic heart failure(HF), is induced by Ang II type 1 receptors(AT1Rs). The AT1R is a G protein-coupled receptor, mainly coupling to Gq/11 proteins. However, it can also signal through β-arrestin-1(βarr1) or-2(βarr2), both of which mediate G protein-independent signaling. Over the past decade, a second, Gq/11 proteinindependent but βarr1-dependent signaling pathway emanating from the adrenocortical AT1R and leading to aldosterone production has become appreciated. Thus, it became apparent that AT1R antagonists that block both pathways equally well are warranted for fully effective aldosterone suppression in HF. This spurred the comparison of all of the currently marketed angiotensin receptor blockers(ARBs, AT1R antagonists or sartans) at blocking activation of the two signaling modes(G protein-, and βarr1-dependent) at the Ang IIactivated AT1R and hence, at suppression of aldosterone in vitro and in vivo. Although all agents are very potent inhibitors of G protein activation at the AT1R, candesartan and valsartan were uncovered to be the most potent ARBs at blocking βarr activation by Ang II and at suppressing aldosterone in vitro and in vivo in post-myocardial infarction HF animals. In contrast, irbesartan and losartan are virtually G protein-"biased" blockers at the human AT1R, with very low efficacy for βarr inhibition and aldosterone suppression. Therefore, candesartan and valsartan(and other, structurally similar compounds) may be the most preferred ARB agents for HF pharmacotherapy, as well as for treatment of other conditions characterized by elevated aldosterone.
文摘目的评估螺内酯对胰岛素以及糖代谢的影响。方法通过检索PubMed、Web of Science、Embase、ClinicalTrials数据库,收集截至2016年3月的相关文献,纳入探究螺内酯对胰岛素敏感性或血糖影响的随机对照试验。结果共有20项随机平行对照以及随机交叉对照试验被纳入。Meta分析结果显示:螺内酯不影响空腹血糖水平[标准化均数差(SMD)为-0.03(95%CI:-0.18~0.12)]、空腹胰岛素水平[SMD为-0.04(95%CI:-0.24~0.16)]或胰岛素抵抗指数[SMD为-0.09(95%CI:-0.24~0.06)],随机平行对照试验合并的糖化血红蛋白SMD为0.03(95%CI:-0.23~0.28)。结论螺内酯对空腹血糖、空腹胰岛素、胰岛素抵抗指数以及糖化血红蛋白均无明显影响。有糖代谢紊乱风险的患者使用螺内酯相对安全,并不会进一步加重糖代谢紊乱或胰岛素抵抗。
