Extracellular renal guanosine cyclic 3'5'-monophosphate modulates nitric oxide and pressure-induced natriuresis.
Extracellular renal guanosine cyclic 3'5'-monophosphate modulates nitric oxide and pressure-induced natriuresis.
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细胞外肾鸟苷环 35-单磷酸调节一氧化氮和压力诱导的尿钠排泄。
DOI：
10.1161/hypertensionaha.107.092973
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Carey,RobertM
中科院分区：
文献类型：
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作者：
Ahmed,Farah;Kemp,BrandonA;Howell,NancyL;Siragy,HelmyM;Carey,RobertM
本研究提出了一种假说，即当鸟苷环3′，5 ′-单磷酸（cGMP）被阻止转运到其肾合成细胞外时，NO和压力诱导的钠尿排泄被抑制。大鼠肾间质注射NO供体S-亚硝基-N-乙酰青霉胺（SNAP）或SNAP+有机阴离子转运体抑制剂丙磺舒（PB）或SNAP+PB+cGMP。单用SNAP可增加UNaV（1小时P<0.05，2小时P <0.005）。与此相反，SNAP不能增加UNaV时，与PB共输注，但cGMP与SNAP+丙磺舒共输注恢复利钠反应。在第二个实验周期，SNAP单独增加RI cGMP（P<0.05）。PB可抑制SNAP引起的RI升高（P<0.01），但与cGMP共输可使cGMP水平恢复。PB也能抑制SNAP引起的Na+（FENa）和锂（FELi）排泄分数的增加（P均<0.01）。PB还取消了RI cGMP和尿钠排泄的上升引起的肾灌注压（RPP）从100至160毫米汞柱的大鼠进行了标准的压力，尿钠排泄协议和钠尿反应的covinjection与cGMP获救。静脉注射磷酸二酯酶V（PDE V）可同时降低RIcGMP和UNa V（P <0.01），但不改变RIcAMP。数据表明，出口cGMP从其肾合成细胞到细胞外RI室是至关重要的利钠作用的NO供体SNAP或增加RPP和RI cGMP控制基础Na+排泄。细胞外cGMP调节NO和压力诱导的尿钠排泄。
This study addresses the hypothesis that NO- and pressure-induced natriuresis are inhibited when guanosine cyclic 3′,5′-monophosphate (cGMP) is prevented from being transported outside its renal synthesizing cells in vivo. Rats received a renal interstitial (RI) infusion of NO donor S-nitroso-N-acetylpenicillamine (SNAP) or SNAP+organic anion transporter inhibitor probenecid (PB) or SNAP+PB+cGMP. SNAP alone increased UNaV (P<0.05 at 1 hour andP<0.005 at 2 hours). In contrast, SNAP failed to increase UNaV when coinfused with PB, but cGMP coinfused with SNAP+probenecid restored the natriuretic response. SNAP alone increased RI cGMP (P<0.05) during the second experimental period. PB abolished the increase in RI cGMP in response to SNAP (P<0.01), but cGMP levels were restored by coinfusion with cGMP. PB also abolished SNAP-induced increases in fractional excretion of Na+(FENa) and lithium (FELi) (bothP<0.01). PB also abolished the rise in RI cGMP and natriuresis induced by raising renal perfusion pressure (RPP) from 100 to 160 mm Hg in rats subjected to a standard pressure-natriuresis protocol and the natriuretic response was rescued by coinfusion with cGMP. RI administration of phosphodiesterase type V (PDE V) reduced both RIcGMP and UNaV in parallel (bothP<0.01) without altering RIcAMP. The data demonstrate that export of cGMP from its renal synthesizing cells into the extracellular RI compartment is critical for the natriuretic action of NO donor SNAP or increased RPP and that RI cGMP controls basal Na+excretion. Extracellular cGMP modulates NO- and pressure-induced natriuresis.