Visscher C A, de Zeeuw D, de Jong P E, Piers D A, Beekhuis H, Groothuis G M, Huisman R M
Department of Medicine, Groningen Institute for Drug Studies, University Hospital, The Netherlands.
J Nucl Med. 1996 Mar;37(3):482-8.
We studied the mechanism of angiotensin-converting enzyme (ACE) inhibition-induced changes in hippurate renography of the poststenotic kidney.
Ten male mongrel dogs, six with unilateral and four with bilateral renal artery stenosis, were equipped with renal artery blood flow probes and catheters in the aorta, atrium and both renal veins.
Enalaprilat (10 mg intravenously) in conscious dogs with renal artery stenoses produced changes in all stenotic (n = 11) but not in nonstenotic kidney 123I-hippurate renograms (n = 6). Renographic changes correlated significantly with initiation of intrarenal 131I-hippurate retention, a decrease in mean arterial pressure (MAP), renal extraction of 131I-hippurate and 125I-iothalamate (r = 0.68, r = 0.62, r = 0.84, r = 0.83, respectively) but not with renal blood flow changes (r = 0.34). Furthermore, renal uptake of 131I-hippurate and 125I-iothalamate decreased in stenotic kidneys with a grade II renogram (-52 +/- 11% and -79 +/- 6%, respectively). Iodine-125-hippurate autoradiograms of stenotic kidneys during ACE inhibition showed tracer retention mainly in the proximal tubular cells. Results during osmotic diuresis supported our findings.
Angiotensin-converting enzyme inhibition-induced hippurate retention curves of poststenotic kidneys appear to result from a sequence of events. A decrease in MAP combined with efferent vasodilation leads to a decrease in intraglomerular capillary pressure. This decrease in pressure causes a decrease in glomerular filtration rate and proximal tubular urine flow. This decrease in turn hampers tubular hippurate transit and transport across the luminal membrane, leading to intrarenal hippurate retention and, in more severe cases, decreased renal hippurate uptake.
我们研究了血管紧张素转换酶（ACE）抑制诱导的狭窄后肾脏马尿酸盐肾图变化的机制。
10只雄性杂种犬，6只单侧肾动脉狭窄，4只双侧肾动脉狭窄，在肾动脉、主动脉、心房和双侧肾静脉中安装肾动脉血流探头和导管。
在有意识的肾动脉狭窄犬中静脉注射依那普利拉（10mg），所有狭窄肾脏（n = 11）的123I-马尿酸盐肾图出现变化，但非狭窄肾脏（n = 6）未出现变化。肾图变化与肾内131I-马尿酸盐潴留的开始、平均动脉压（MAP）降低、131I-马尿酸盐和125I-碘他拉酸盐的肾摄取显著相关（分别为r = 0.68、r = 0.62、r = 0.84、r = 0.83），但与肾血流变化无关（r = 0.34）。此外，肾图为II级的狭窄肾脏中131I-马尿酸盐和125I-碘他拉酸盐的肾摄取减少（分别为-52±11%和-79±6%）。ACE抑制期间狭窄肾脏的碘-125-马尿酸盐放射自显影片显示示踪剂主要保留在近端肾小管细胞中。渗透性利尿期间的结果支持了我们的发现。
血管紧张素转换酶抑制诱导的狭窄后肾脏马尿酸盐潴留曲线似乎是一系列事件的结果。MAP降低与出球小动脉扩张相结合导致肾小球毛细血管压力降低。压力降低导致肾小球滤过率和近端肾小管尿流减少。这种减少反过来阻碍肾小管马尿酸盐转运和跨腔膜运输，导致肾内马尿酸盐潴留，在更严重的情况下，肾马尿酸盐摄取减少。
