Department of Physiology, School of Medical Sciences, University of Otago, PO Box 913, Dunedin, New Zealand.
Pflugers Arch. 2014 Mar;466(3):459-66. doi: 10.1007/s00424-013-1338-5. Epub 2013 Aug 25.
Despite advances in our understanding concerning the pathology of hypertension, the mechanisms that underpin the origin of hypertension remain to be fully elucidated. This enigma is, at least in part, due to inherent limitations of various animal models of hypertension. Here, we show the genetically modified Cyp1a1-Ren2 rat model, in which the onset and severity of angiotensin II-dependent hypertension can be tightly controlled, as an effective model for investigating increased sympathetic drive for the onset of hypertension. Cyp1a1-Ren2 rats were surgically prepared with radiotelemetric transmitters for the continuous measurement of arterial blood pressure (ABP). ABP was recorded in freely moving rats that were fed with either normal rat chow or a diet containing indole-3-carbinol (0.225% w/w) for 7 days to induce hypertension. Structural morphology of and endothelial NO synthase (eNOS) protein expression in heart and/or vascular tissue were analyzed. Sympathetic tone was estimated using spectral analysis of heart rate variability. The progressive induction of hypertension over 7 days was matched with a parallel increase in sympathetic tone. By day 7 of hypertension, eNOS expression in the mesenteric artery was elevated. However, the elevated ABP, sympathetic tone, and eNOS had not elicited gross morphological remodeling of the heart or vasculature. Importantly, both the increase in sympathetic tone and overexpression of eNOS within the vasculature were reversed when ABP was returned to normal. We conclude that the Cyp1a1-Ren2 rat provides an effective model for investigating specific adverse and transient changes in central sympathetic modulation of arterial blood pressure during the early onset of angiotensin-dependent hypertension.
尽管我们在高血压病理学方面的认识有所进步，但支持高血压起源的机制仍有待充分阐明。这种谜团至少部分归因于各种高血压动物模型固有的局限性。在这里，我们展示了经过基因改造的 Cyp1a1-Ren2 大鼠模型，该模型可以严格控制血管紧张素 II 依赖性高血压的发作和严重程度，是研究交感神经驱动增加与高血压发作的有效模型。Cyp1a1-Ren2 大鼠通过放射性遥测发射器进行手术准备，以连续测量动脉血压 (ABP)。在自由活动的大鼠中记录 ABP，这些大鼠喂食正常大鼠饲料或含有吲哚-3-甲醇（0.225%w/w）的饮食 7 天以诱导高血压。分析心脏和/或血管组织的结构形态和内皮型一氧化氮合酶 (eNOS) 蛋白表达。使用心率变异性的频谱分析来估计交感神经张力。7 天内高血压的逐渐诱导与交感神经张力的平行增加相匹配。在高血压的第 7 天，肠系膜动脉中的 eNOS 表达升高。然而，升高的 ABP、交感神经张力和 eNOS 并没有引起心脏或血管的大体形态重塑。重要的是，当 ABP 恢复正常时，血管内的交感神经张力增加和 eNOS 的过表达都得到了逆转。我们得出结论，Cyp1a1-Ren2 大鼠为研究血管紧张素依赖性高血压早期发作时动脉血压中枢交感神经调节的特定不良和短暂变化提供了有效模型。
