Angiotensin type 2 receptor mediates valsartan-induced hypotension in conscious rats
Angiotensin type 2 receptor mediates valsartan-induced hypotension in conscious rats
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DOI：
10.1161/01.hyp.35.5.1074
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发表时间：
2000-05-01
期刊：
影响因子：
8.3
通讯作者：
Carey, RM
中科院分区：
文献类型：
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作者：
Siragy, HM;de Gasparo, M;Carey, RM
肾素-血管紧张素系统的抑制与血管扩张和血压下降有关，我们假设血管紧张素1型(AT(1))受体(AT(1)R)的阻断与缓激素(BK)释放介导的肾脏一氧化氮(NO)的产生增加有关。应用微透析技术监测静脉注射血管紧张素转换酶(AT(1)R)阻滞剂valsartan(10 mg/kg)、血管紧张素2(AT(2)R)受体(AT(2)R)阻滞剂PD123319(50 mU·g.Kg(-1)。Min(-1))和BK B-2受体阻滞剂icatibant(10微克)。Kg(-1)。Min(-1))，清醒大鼠(n=10)在低钠摄入时。在valsartan治疗期间，RIF BK、NOX和cGMP显著升高，而AT(2)R阻断则导致这些耳廓的显著下降。输注过程中，RIF NOX和cGMP分别下降了%和40%，而BK升高。联合应用valsartan和icatibant，valsartan和PD123319，或valsartan，PD123319和icatibant可阻止单独应用valsartan时RIF、cGMP和NOx的增加。这些数据表明，用valsartan阻断AT(1)R与肾BK的释放有关，而BK的释放又介导了NO的产生。结果提示，血管紧张素II的增加，作为钠限制和输注valsartan的反应，刺激AT(2)R，从而介导BK而不是级联反应。
Inhibition of the renin-angiotensin system is associated with vasodilation and reduction in blood pressure, We hypothesized that angiotensin type 1 (AT(1)) receptor (AT(1)R) blockade is associated with increased production of renal nitric oxide (NO) mediated by release of bradykinin (BK). By use of a microdialysis technique, changes in renal interstitial fluid (RIF) BK, NO end products nitrite and nitrate (NOX), and cGMP were monitored in response to intravenous infusion of the AT(1)R blocker valsartan (10 mg/kg), the angiotensin type 2 (AT(2)) receptor (AT(2)R) blocker PD123319 (50 mu g . kg(-1) . min(-1)), and the BK B-2 receptor blocker icatibant (10 mu g . kg(-1) . min(-1)) in conscious rats (n=10) during low sodium intake. RIF BK, NOX, and cGMP significantly increased during valsartan treatment, whereas AT(2)R blockade caused a significant decrease in these autacoids. During icatibant infusion, RIF NOX and cGMP decreased by 64% and 40%, respectively, whereas BK increased. Combined administration of valsartan and icatibant, of valsartan and PD123319, or of valsartan, PD123319, and icatibant prevented the increase in RIF cGMP and NOX in response to valsartan alone. These data demonstrate that AT(1)R blockade with valsartan is associated with release of renal BK, which in turn mediates NO production. The results suggest that increased angiotensin II, in response to sodium restriction and valsartan infusion, stimulates AT(2)R, which mediates a BK and NO cascade.