Increased activity of cGMP-specific phosphodiesterase (PDE5) contributes to resistance to atrial natriuretic peptide natriuresis in the pregnant rat.
Increased activity of cGMP-specific phosphodiesterase (PDE5) contributes to resistance to atrial natriuretic peptide natriuresis in the pregnant rat.
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cGMP 特异性磷酸二酯酶 (PDE5) 活性的增加有助于妊娠大鼠对心房钠尿肽的钠排泄抵抗。
DOI：
10.1097/01.asn.0000125613.96927.38
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Humphreys,MichaelH
中科院分区：
文献类型：
--
作者：
Ni,Xi-Ping;Safai,Massy;Rishi,Rahul;Baylis,Chris;Humphreys,MichaelH
肾内髓质集合管(IMCD)细胞cGMP特异性磷酸二酯酶(PDE5)活性升高是实验性肾病综合征和肝硬变患者对心钠素(ANP)的抵抗和钠离子过度滞留的原因之一。正常妊娠还伴有钠滞留和血浆容量扩张，怀孕大鼠对心钠素的利钠作用有抵抗力。作者调查了肾脏PDE5活性增加在正常大鼠妊娠生理性钠滞留中的可能作用。在16d孕鼠和处女大鼠中，由急性容量扩张(衡量肾脏对内源性ANP的反应性)引起的钠尿和尿中cGMP排泄增加(U CGMP V)是钝化的，尽管孕鼠和处女的循环ANP同样增加。体外培养的妊娠IMCD细胞对心钠素依赖的cGMP积聚被钝化，并被PDE5选择性拮抗剂DMPPO(10−7mol/L)恢复。妊娠组的PDE5体外活性和IMCD中的PDE5蛋白丰度较高。产后4天，IMCD细胞匀浆中容量扩张性钠尿量、U cGMP V和PDE5蛋白水平恢复至原始水平。这些结果表明，正常大鼠妊娠导致体内和体外肾脏对ANP的抵抗，这与IMCD中cGMP特异性PDE5的活性增强有关。这可能与正常妊娠的生理性钠滞留有关。
Increased cGMP-specific phosphodiesterase (PDE5) activity in renal inner medullary collecting duct (IMCD) cells contributes to resistance to atrial natriuretic peptide (ANP) and the excessive sodium retention seen in experimental nephrotic syndrome and liver cirrhosis. Normal pregnancy is also accompanied by sodium retention and plasma volume expansion, and pregnant rats are resistant to the natriuretic action of ANP. The authors investigated a possible role of increased renal PDE5 activity in the physiologic sodium retention of normal rat pregnancy. The natriuresis and increased urinary cGMP excretion (U cGMP V) evoked by acute volume expansion (a measure of renal responsiveness to endogeneous ANP) was blunted in 16-d pregnant versus virgin rats, despite equivalent increases in circulating ANP in pregnants and virgins. The ANP-dependent cGMP accumulation in isolated IMCD cells from pregnants was blunted versus virgins and restored by the PDE5-selective antagonist DMPPO (10− 7 mol/L). PDE5 activity in vitro and PDE5 protein abundance in IMCD were greater in pregnants. Four days postpartum, volume expansion natriuresis, U cGMP V, and PDE5 protein levels in IMCD cell homogenates had returned to virgin values. These results demonstrate that normal rat pregnancy leads to in vivo and in vitro renal resistance to ANP, in association with heightened activity of the cGMP-specific PDE5 in IMCD. This may contribute to the physiologic sodium retention of normal pregnancy.