Rahmouni K, Barthelmebs M, Imbs J L, De Jong W
Institut de pharmacologie, Faculté de médecine, Université Louis-Pasteur, Strasbourg.
Arch Mal Coeur Vaiss. 1998 Aug;91(8):1009-12.
Brain control of arterial blood pressure in man and in animals has been studied increasingly over the last few decades. Despite our knowledge about short term regulation (chemoreceptor and baroreceptor reflexes) there is much more uncertainty about the degree of involvement of brain mechanisms in long term control of blood pressure, and in hypertension. The last decade, a role of brain mineralocorticoid receptors (MR) has been outlined in animal experiments. Stimulation of brain MR by aldosterone or related mineralocorticoids induces an increase in blood pressure and hypertension under chronic conditions. These effects of mineralocorticoid excess can be blocked by specific MR antagonists administered centrally. Stimulation of brain glucocorticoid receptors, as compared to stimulation of brain MR, has an opposite effect, i.e. decreases blood pressure. As in the typical peripheral target organs of aldosterone, in the brain, enzymatic protection of MR against glucocorticoids appears to play an important role. We showed that in conscious normotensive rats intracerebroventricular (i.c.v.) injection of a specific MR antagonist (RU28318) in a low dose (10 ng) decreases blood pressure by about 20% without affecting heart rate. A similar but smaller effect (not statistically significant) was observed in conscious female rats. Only in the male rats an increased diuresis occurred and this may have contributed to the observed hypotension. We conclude that hypertension caused by mineralocorticoid excess may depend on a concerted action of the steroid on the kidney and on the brain. The mechanism by which brain MR increases blood pressure is unknown. It is possible that increased sympathetic outflow and renal mechanisms are involved. Interference with brain MR not only affects blood pressure but it also has effect on renal function.
在过去几十年里,对人和动物大脑对动脉血压的控制研究越来越多。尽管我们了解短期调节(化学感受器和压力感受器反射),但大脑机制在血压长期控制以及高血压中的参与程度仍存在更多不确定性。在过去十年中,动物实验已阐明大脑盐皮质激素受体(MR)的作用。在慢性条件下,醛固酮或相关盐皮质激素刺激大脑MR会导致血压升高和高血压。盐皮质激素过量的这些作用可被中枢给予的特异性MR拮抗剂阻断。与刺激大脑MR相比,刺激大脑糖皮质激素受体具有相反的作用,即降低血压。与醛固酮典型的外周靶器官一样,在大脑中,MR对糖皮质激素的酶促保护似乎起着重要作用。我们发现,在清醒的正常血压大鼠中,脑室内(i.c.v.)注射低剂量(10 ng)的特异性MR拮抗剂(RU28318)可使血压降低约20%,而不影响心率。在清醒的雌性大鼠中观察到类似但较小的作用(无统计学意义)。仅在雄性大鼠中出现利尿增加,这可能是观察到的低血压的原因之一。我们得出结论,盐皮质激素过量引起的高血压可能取决于该类固醇在肾脏和大脑上的协同作用。大脑MR升高血压的机制尚不清楚。可能涉及交感神经流出增加和肾脏机制。干扰大脑MR不仅会影响血压,还会对肾功能产生影响。