Wang Hao, Huang Bing S, Leenen Frans H H
Hypertension Unit, University of Ottawa Heart Institute, Ottawa, Ontario, Canada K1Y 4W7.
Am J Physiol Heart Circ Physiol. 2003 Dec;285(6):H2516-23. doi: 10.1152/ajpheart.00299.2003. Epub 2003 Aug 21.
Central nervous system (CNS) effects of mineralocorticoids participate in the development of salt-sensitive hypertension. In the brain, mineralocorticoids activate amiloride-sensitive sodium channels, and we hypothesized that this would lead to increased release of ouabainlike compounds (OLC) and thereby sympathetic hyperactivity and hypertension. In conscious Wistar rats, intracerebroventricular infusion of aldosterone at 300 or 900 ng/h in artificial cerebrospinal fluid (aCSF) with 0.145 M Na+ for 2 h did not change baseline mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), or heart rate (HR). Intracerebroventricular infusion of aCSF containing 0.16 M Na+ (versus 0.145 M Na+ in regular aCSF) did not change MAP or RSNA, but significant increases in MAP, RSNA, and HR were observed after intracerebroventricular infusion of aldosterone at 300 ng/h for 2 h. Intracerebroventricular infusion of aCSF containing 0.3 M Na+ increased MAP, RSNA, and HR significantly more after intracerebroventricular infusion of aldosterone versus vehicle. After intracerebroventricular infusion of aldosterone, the MAP, RSNA, and HR responses to intracerebroventricular infusion of aCSF containing 0.16 M Na+ were blocked by blockade of brain OLC with intracerebroventricular infusion of Fab fragments or of brain sodium channels with intracerebroventricular benzamil. Chronic intracerebroventricular infusion of aldosterone at 25 ng/h in aCSF with 0.15 M Na+ for 2 wk increased MAP by 15-20 mmHg and increased hypothalamic OLC by 30% and pituitary OLC by 60%. Benzamil blocked all these responses to aldosterone. These findings indicate that in the brain, mineralocorticoids activate brain sodium channels, with small increases in CSF Na+ leading to increases in brain OLC, sympathetic outflow, and blood pressure.
盐皮质激素对中枢神经系统（CNS）的影响参与了盐敏感性高血压的发展。在大脑中，盐皮质激素激活阿米洛利敏感的钠通道，我们推测这会导致哇巴因样化合物（OLC）释放增加，从而引起交感神经过度活跃和高血压。在清醒的Wistar大鼠中，在含0.145 M Na⁺的人工脑脊液（aCSF）中以300或900 ng/h的速度脑室内注入醛固酮2小时，并未改变基线平均动脉压（MAP）、肾交感神经活动（RSNA）或心率（HR）。脑室内注入含0.16 M Na⁺的aCSF（相对于常规aCSF中的0.145 M Na⁺）并未改变MAP或RSNA，但在以300 ng/h的速度脑室内注入醛固酮2小时后，观察到MAP、RSNA和HR显著增加。与注入赋形剂相比，脑室内注入含0.3 M Na⁺的aCSF后，再脑室内注入醛固酮会使MAP、RSNA和HR的增加更为显著。脑室内注入醛固酮后，通过脑室内注入Fab片段阻断脑OLC或通过脑室内注入苄amil阻断脑钠通道，可阻断对脑室内注入含0.16 M Na⁺的aCSF的MAP、RSNA和HR反应。在含0.15 M Na⁺的aCSF中以25 ng/h的速度慢性脑室内注入醛固酮2周，可使MAP升高15 - 20 mmHg，使下丘脑OLC增加30%，垂体OLC增加60%。苄amil可阻断所有这些对醛固酮的反应。这些发现表明，在大脑中，盐皮质激素激活脑钠通道，脑脊液Na⁺的小幅增加会导致脑OLC、交感神经输出和血压升高。
