Effect of inhibiting renal kallikrein on prostaglandin E2, water, and sodium excretion.
Effect of inhibiting renal kallikrein on prostaglandin E2, water, and sodium excretion.
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DOI：
10.1161/01.hyp.25.5.1008
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发表时间：
1995-05
期刊：
影响因子：
8.3
通讯作者：
S. Saitoh;A. Scicli;E. Peterson;O. Carretero
中科院分区：
文献类型：
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作者：
S. Saitoh;A. Scicli;E. Peterson;O. Carretero
为了验证肾激肽作为利钠和利尿激素的假设，我们研究了在正常钠摄入量下抑制腺激肽释放酶对正常血压非麻醉大鼠肾功能的影响。为了在远端肾单位的管腔和基底外侧抑制激肽释放酶，我们使用了抗大鼠尿激肽释放酶(FAB-激肽释放酶)的单抗的Fab片段。FAB片段比完整的免疫球蛋白有优势：它们通过肾小球过滤，到达远端肾单位的管腔，激肽释放酶在那里被定位，尿激肽释放。此外，Fab片段-抗原复合体不激活补体系统，避免了与完整抗体相关的副作用。FAB-激肽释放酶有效地阻断了肾单位管腔激肽的生成，使尿激肽原酶活性(激肽释放酶)减少74%至85%，激肽排泄减少76%至79%。FAB-激肽释放酶诱导尿量减少30%，尿钠排泄减少20%-40%，但不改变血压、肾小球滤过率或肾脏血流量。虽然尿前列腺素E_2排泄量也有下降的趋势，但这一变化比激动素和激肽原酶排泄的变化慢且幅度小，经Bonferroni‘s校正后无统计学意义。在注射了抗蓖麻毒素(一种哺乳动物中不存在的植物蛋白)的单抗的载体或Fab片段的对照组中，这些参数都没有显著下降。我们的结论是，肾激肽作为利尿剂和利钠激素参与了血压正常的非麻醉大鼠短期水和钠排泄的调节。
To test the hypothesis that renal kinins act as natriuretic and diuretic hormones, we examined the effect of inhibiting glandular kallikrein on renal function in normotensive unanesthetized rats during normal sodium intake. To inhibit kallikrein at both the luminal and basolateral sides of the distal nephron, we used Fab fragments of monoclonal antibodies to rat urinary kallikrein (Fab-kallikrein). Fab fragments have advantages over intact IgG: they are filtered through the glomerulus and reach the lumen of the distal nephron, where kallikrein is localized and urinary kinins are released. Furthermore, the Fab fragment-antigen complex does not activate the complement system, avoiding the side effects associated with intact antibodies. Fab-kallikrein effectively blocked generation of kinins in the nephron lumen, decreasing urinary kininogenase activity (kallikrein) by 74% to 85% and kinin excretion by 76% to 79%. Fab-kallikrein induced a 30% decrease in urine volume and a 20% to 40% decrease in urinary sodium excretion but did not alter blood pressure, glomerular filtration rate, or renal blood flow. Although urinary prostaglandin E2 excretion also tended to decrease, this change was slower and of lesser magnitude than those of kinin and kininogenase excretion and did not attain statistical significance after Bonferroni's correction. In controls injected with either vehicle or Fab fragments of monoclonal antibodies to ricin (a vegetable protein not present in mammals), none of these parameters decreased significantly. We conclude that renal kinins participate in the short-term regulation of water and sodium excretion in normotensive unanesthetized rats, acting as diuretic and natriuretic hormones.(ABSTRACT TRUNCATED AT 250 WORDS)