Reinforcing feedback loop of renal cyclic guanosine 3' 5' -monophosphate and interstitial hydrostatic pressure in pressure-natriuresis.
Reinforcing feedback loop of renal cyclic guanosine 3' 5' -monophosphate and interstitial hydrostatic pressure in pressure-natriuresis.
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DOI：
10.1161/hypertensionaha.109.131995
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发表时间：
2009-12
期刊：
影响因子：
--
通讯作者：
Carey RM
中科院分区：
文献类型：
--
作者：
Lieb DC;Kemp BA;Howell NL;Gildea JJ;Carey RM
本研究阐明了肾间质环鸟苷酸（cGMP）通过与肾间质流体静压（RIHP）的关系发挥其作用的假说。增加Sprague-Dawley大鼠的肾灌注压（RPP）导致RIHP增加（5.2 ± 0.6至10.9 ± 1.6 mm Hg; P <0.01），UNaV（0.062 ± 0.009~0.420 ± 0.068 μ mol/min/g; P <0.01），RI cGMP（3.5 ± 0.8~9.5 ± 1.7 fmol/min; P <0.01），这些作用可被部分肾去膜阻断。再灌注cGMP可使去冠动物的尿钠排泄恢复（0.067 ± 0.010~0.310 ± 0.061 μ mol/min/g; P <0.01）。这些变化独立于肾小球滤过率（GFR）的变化。在正常血压动物中，随着RIHP的增加，RI cGMP（4.1 ± 0.6~6.9 ± 0.7fmol/min; P <0.01）和UNaV（0.071 ± 0.013~0.179 ± 0.039 μ mol/min/g; P <0.05）也增加。共同输注有机阴离子转运抑制剂丙磺舒，或可溶性鸟苷酸环化酶抑制剂ODQ，取消这些影响。将cGMP注入正常血压动物的RI室中可增加RIHP（6.7 ± 0.4至10.3 ± 0.9 mm Hg; P <0.001）。外源性RI cGMP输送不影响总的，皮质，或髓质肾血流量。这些研究表明，RPP和RIHP增加后观察到的钠尿排泄需要细胞外RI cGMP，cGMP通过小管机制起作用。结果支持肾内正反馈回路，其中RI cGMP增加RIHP，RIHP又增加RI cGMP，有助于P-N的增强。
This study addresses the hypothesis that renal interstitial (RI) cyclic guanosine 3′5′-monophosphate (cGMP), a modulator of pressure-natriuresis (P-N), exerts its effect through a relationship with renal interstitial hydrostatic pressure (RIHP). Increasing renal perfusion pressure (RPP) in Sprague-Dawley rats led to increases in RIHP (5.2 ± 0.6 to 10.9 ± 1.6 mm Hg; P<0.01), UNaV (0.062 ± 0.009 to 0.420 ± 0.068 μmol/min/g; P<0.01), and RI cGMP (3.5 ± 0.8 to 9.5 ± 1.7 fmol/min; P<0.01), and these effects were blocked by partial renal decapsulation. Infusion of cGMP into the RI compartment of decapsulated animals restored natriuresis (0.067 ± 0.010 to 0.310 ± 0.061 μmol/min/g; P<0.01). These changes were independent of changes in glomerular filtration rate (GFR). Artificially increasing RIHP in normotensive animals increased RI cGMP (4.1 ± 0.6 to 6.9 ± 0.7 fmol/min; P<0.01) and UNaV (0.071 ± 0.013 to 0.179 ± 0.039 μmol/min/g; P<0.05). Co-infusion of organic anion transport-inhibitor probenecid, or soluble guanylyl cyclase inhibitor ODQ, abolished these effects. Infusion of cGMP into the RI compartment of normotensive animals increased RIHP (6.7 ± 0.4 to 10.3 ± 0.9 mm Hg; P<0.001). Exogenous RI cGMP delivery did not affect total, cortical, or medullary renal blood flow. These studies suggest that extracellular RI cGMP is required for the natriuresis observed after increases in RPP and RIHP, and that cGMP acts via a tubule mechanism. The results support an intra-renal positive-feedback loop wherein RI cGMP increases RIHP, which in turn increases RI cGMP, contributing to the reinforcement of P-N.