Departments of Physiology and Medicine, University of Florida, Gainesville, Florida.
Am J Hypertens. 2013 Oct;26(10):1242-9. doi: 10.1093/ajh/hpt096. Epub 2013 Jun 13.
Dietary administration of 0.30% indole-3-carbinol (I3C) to Cyp1a1-Ren2 transgenic rats (TGRs) generates angiotensin II (ANG II)-dependent malignant hypertension (HTN) and increased renal vascular resistance. However, TGRs with HTN maintain a normal or slightly reduced glomerular filtration rate. We tested the hypothesis that maintenance of renal function in hypertensive Cyp1a1-Ren2 TGRs is due to preservation of the intrarenal nitric oxide (NO) and antioxidant systems.
Kidney cortex, kidney medulla, aortic endothelial (e) and neuronal (n) nitric oxide synthase (NOS), superoxide dismutases (SODs), and p22phox (nicotinamide adenine dinucleotide phosphate-oxidase subunit) protein abundances were measured along with kidney cortex total antioxidant capacity (TAC) and NOx. TGRs were fed a normal diet that contained 0.3% I3C or 0.3% I3C + candesartan (AT1 receptor antagonist; 25mg/L in drinking water) (n = 5-6 per group) for 10 days.
Blood pressure increased and body weight decreased in I3C-induced TGRs, while candesartan blunted these responses. Abundances of NOS, SOD, and p22phox as well as TAC were maintained in the kidney cortex of I3C-induced TGRs with and without candesartan, while kidney cortex NOx production increased in both groups. Kidney medulla eNOS and extracellular (EC) SOD decreased and nNOS were unchanged in both groups of I3C-induced TGRs. In addition, a compensatory increase occurred in kidney medulla Mn SOD in I3C-induced TGRs + candesartan. Aortic eNOS and nNOS∝ fell and p22phox and Mn SOD increased in hypertensive I3C-induced TGRs; all changes were reversed with candesartan.
The preservation of renal cortical NO and antioxidant capacity is associated with preserved renal function in Cyp1a1-Ren2 TGRs with ANG II-dependent malignant HTN.
给 Cyp1a1-Ren2 转基因大鼠（TGRs）喂食 0.30%吲哚-3-甲醇（I3C）会产生血管紧张素 II（ANG II）依赖性恶性高血压（HTN）和增加肾血管阻力。然而，患有 HTN 的 TGRs 保持正常或略低的肾小球滤过率。我们检验了这样一个假设，即 Cyp1a1-Ren2 TGRs 中高血压的维持是由于肾内一氧化氮（NO）和抗氧化系统的保存。
测量肾脏皮质、肾脏髓质、主动脉内皮（e）和神经元（n）一氧化氮合酶（NOS）、超氧化物歧化酶（SOD）和 p22phox（烟酰胺腺嘌呤二核苷酸磷酸氧化酶亚单位）的蛋白丰度，以及肾脏皮质总抗氧化能力（TAC）和 NOx。TGRs 喂食含有 0.3%I3C 的正常饮食或含有 0.3%I3C 和坎地沙坦（AT1 受体拮抗剂；饮用水中 25mg/L）的饮食（每组 5-6 只）10 天。
I3C 诱导的 TGRs 血压升高，体重下降，而坎地沙坦则减轻了这些反应。在 I3C 诱导的 TGRs 中，无论是否使用坎地沙坦，NOS、SOD 和 p22phox 的丰度以及 TAC 均保持在肾脏皮质中，而两组的肾脏皮质 NOx 生成均增加。两组 I3C 诱导的 TGRs 中，肾脏髓质 eNOS 和细胞外（EC）SOD 减少，nNOS 不变。此外，在 I3C 诱导的 TGRs +坎地沙坦中，肾脏髓质 Mn SOD 代偿性增加。高血压 I3C 诱导的 TGRs 中，主动脉 eNOS 和 nNOS∝下降，p22phox 和 Mn SOD 增加；所有变化均被坎地沙坦逆转。
在 Cyp1a1-Ren2 TGRs 中，ANG II 依赖性恶性 HTN 与肾皮质 NO 和抗氧化能力的保存有关。
