Dept. of Physiology, Tulane Univ. Health Sciences Center, 1430 Tulane Ave., SL39, New Orleans, LA 70112, USA.
Am J Physiol Renal Physiol. 2012 Jan 1;302(1):F52-9. doi: 10.1152/ajprenal.00187.2011. Epub 2011 Oct 12.
Angiotensin (ANG) II-dependent hypertension is characterized by increases in intrarenal ANG II levels, derangement in renal hemodynamics, and augmented tubular sodium reabsorptive capability. Increased nephron expression of renin-angiotensin system components, such as angiotensinogen by proximal tubule cells and renin by collecting duct principal cells, has been associated with an augmented ability of the kidney to form ANG II in hypertensive states. However, the contribution of de novo intrarenal ANG II production to the development and maintenance of ANG II-dependent hypertension remains unclear. The present study was performed to determine the effects of selective intrarenal renin inhibition on whole kidney hemodynamics and renal excretory function in Cyp1a1-Ren2 rats with ANG II-dependent malignant hypertension in the absence of the confounding influence of associated reductions in mean arterial pressure (MAP). Male Cyp1a1-Ren2 transgenic rats were induced to develop malignant hypertension, anesthetized, and surgically prepared for intrarenal administration of the direct renin inhibitor aliskiren (0.01 mg/kg). Following acute aliskiren treatment, urine flow and sodium excretion increased (10.5 ± 1.1 to 15.9 ± 1.9 μl/min, P < 0.001; 550 ± 160 to 1,370 ± 320 neq/min, P < 0.001, respectively) and ANG II excretion decreased (120 ± 30 to 63 ± 17 fmol/h, P < 0.05). There were no significant changes in MAP, glomerular filtration rate, estimated renal plasma flow, plasma ANG II levels, or protein excretion. The present findings demonstrate that selective renal renin inhibition elicits diuretic and natriuretic responses in Cyp1a1-Ren2 rats with ANG II-dependent malignant hypertension. Elevated intraluminal ANG II levels likely act to augment tubular reabsorptive function and, thereby, contribute to the elevated blood pressure in Cyp1a1-Ren2 rats with ANG II-dependent malignant hypertension.
血管紧张素（ANG）II 依赖性高血压的特征是肾内 ANG II 水平升高、肾血流动力学紊乱以及肾小管钠重吸收能力增强。近端肾小管细胞中血管紧张素原和集合管主细胞中肾素等肾素-血管紧张素系统成分的肾单位表达增加，与高血压状态下肾脏形成 ANG II 的能力增强有关。然而，内源性 ANG II 产生在 ANG II 依赖性高血压的发展和维持中的贡献仍不清楚。本研究旨在确定选择性肾内肾素抑制对 Cyp1a1-Ren2 大鼠 ANG II 依赖性恶性高血压时整个肾脏血液动力学和肾脏排泄功能的影响，该大鼠在没有相关平均动脉压（MAP）降低的混杂影响的情况下。雄性 Cyp1a1-Ren2 转基因大鼠诱导发生恶性高血压，麻醉并进行手术准备，以进行直接肾素抑制剂阿利克仑（0.01 mg/kg）的肾内给药。急性阿利克仑治疗后，尿流量和钠排泄增加（10.5 ± 1.1 至 15.9 ± 1.9 μl/min，P < 0.001；550 ± 160 至 1370 ± 320 neq/min，P < 0.001），ANG II 排泄减少（120 ± 30 至 63 ± 17 fmol/h，P < 0.05）。MAP、肾小球滤过率、估计肾血浆流量、血浆 ANG II 水平或蛋白排泄均无显著变化。本研究结果表明，选择性肾内肾素抑制在 Cyp1a1-Ren2 大鼠 ANG II 依赖性恶性高血压中引起利尿和排钠反应。升高的管腔内 ANG II 水平可能增强管状重吸收功能，从而有助于 Cyp1a1-Ren2 大鼠 ANG II 依赖性恶性高血压中的高血压。
