Department of Psychology, Cardiovascular Center, University of Iowa, 11 Seashore Hall E, Iowa City, IA 52242, USA.
Hypertension. 2012 Oct;60(4):1023-30. doi: 10.1161/HYPERTENSIONAHA.112.196576. Epub 2012 Sep 4.
Previous studies have shown that preconditioning rats with a nonpressor dose of angiotensin II (Ang II) sensitizes the pressor response produced by later treatment with a higher dose of Ang II and that Ang II and aldosterone (Aldo) can modulate each other's pressor effects through actions involving the central nervous system. The current studies tested whether Aldo can cross-sensitize the pressor actions of Ang II to enhance hypertension by employing an induction-delay-expression experimental design. Male rats were implanted for telemetered blood pressure recording. During induction, subpressor doses of either subcutaneous or intracerebroventricular Aldo were delivered for 1 week. Rats were then rested for 1 week (delay) to assure that any exogenous Aldo was metabolized. After this, Ang II was given subcutaneously for 2 weeks (expression). During induction and delay, Aldo had no sustained effect on blood pressure. However, during expression, Ang II-induced hypertension was greater in the groups receiving subcutaneous or intracerebroventricular Aldo during induction in comparison with those groups receiving vehicle. Central administration of mineralocorticoid receptor antagonist blocked sensitization. Brain tissue collected at the end of delay and expression showed increased mRNA expression of several renin-angiotensin-aldosterone system components in cardiovascular-related forebrain regions of cross-sensitized rats. Cultured subfornical organ neurons preincubated with Aldo displayed greater increases in [Ca2+]i after Ang II treatment, and there was a greater Fra-like immunoreactivity present at the end of expression in cardiovascular-related forebrain structures. Taken together, these results indicate that Aldo pretreatment cross-sensitizes the development of Ang II-induced hypertension probably by mechanisms that involve the central nervous system.
先前的研究表明，用非加压剂量的血管紧张素 II（Ang II）预处理大鼠会使随后用更高剂量的 Ang II 处理产生的升压反应敏感，并且 Ang II 和醛固酮（Aldo）可以通过涉及中枢神经系统的作用来调节彼此的升压作用。目前的研究通过采用诱导-延迟-表达实验设计，测试了 Aldo 是否可以交叉敏化 Ang II 的升压作用，从而增强高血压。雄性大鼠被植入用于遥测血压记录的装置。在诱导期间，给予皮下或脑室内的亚加压剂量的 Aldo 持续 1 周。然后，大鼠休息 1 周（延迟）以确保任何外源性 Aldo 都被代谢掉。在此之后，给予皮下 Ang II 持续 2 周（表达）。在诱导和延迟期间，Aldo 对血压没有持续的影响。然而，在表达期间，与接受载体的组相比，在诱导期间接受皮下或脑室内 Aldo 的组的 Ang II 诱导的高血压更大。中枢给予盐皮质激素受体拮抗剂可阻断敏化作用。延迟和表达结束时收集的脑组织显示，在交叉敏化大鼠的心血管相关前脑区域中，几种肾素-血管紧张素-醛固酮系统成分的 mRNA 表达增加。预先用 Aldo 孵育的下穹窿器官神经元在 Ang II 处理后显示出更大的 [Ca2+]i 增加，并且在心血管相关前脑结构的表达结束时存在更大的 Fra 样免疫反应性。总之，这些结果表明，Aldo 预处理可能通过涉及中枢神经系统的机制交叉敏化 Ang II 诱导的高血压的发展。
