Paton J F R, Dickinson C J, Mitchell G
Department of Physiology & Pharmacology, Bristol Heart Institute, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK.
Exp Physiol. 2009 Jan;94(1):11-7. doi: 10.1113/expphysiol.2008.043455. Epub 2008 Sep 26.
The fundamental mechanism that underlies essential hypertension is a high total peripheral resistance. We review here possible origins of high total peripheral resistance in physiologically hypertensive giraffes, spontaneously hypertensive rats and humans with essential hypertension. We propose that a common link could be reduced brainstem perfusion, as first suggested by Cushing in 1901. Any tendency towards reduction of cerebral blood flow to the cardiovascular control centres in rest and sleep will be prevented by activation of a response arising in the brainstem. The response will proportionately increase systemic blood pressure and return cerebral blood flow to a new homeostatic level. New evidence we review here supports this idea and leads us to suggest that central regulation of blood pressure has two components: the classic Cushing's response, which is a terminal event, and a Cushing's mechanism, which is a physiological mechanism for long-term control of mean arterial pressure. In giraffes, Cushing's mechanism is activated by increasing neck length during growth and subsequent gravitational hypotension that stimulates a rise in basal arterial blood pressure. In man and rats, the mechanism is activated by narrowing of the arteries supplying the brainstem. If we are correct, future successful treatment of essential hypertension in man will include methods of reducing cerebral arterial resistance.
原发性高血压的根本机制是总外周阻力升高。我们在此回顾生理性高血压长颈鹿、自发性高血压大鼠以及原发性高血压患者中总外周阻力升高的可能原因。我们提出，共同的联系可能是脑干灌注减少，这一观点最早由库欣于1901年提出。在休息和睡眠状态下，任何导致流向心血管控制中枢的脑血流量减少的趋势都会被脑干产生的一种反应激活所阻止。这种反应会相应地升高全身血压，并使脑血流量恢复到新的稳态水平。我们在此回顾的新证据支持这一观点，并使我们提出血压的中枢调节有两个组成部分：经典的库欣反应，这是一个终末事件；以及库欣机制，这是一种长期控制平均动脉压的生理机制。在长颈鹿中，库欣机制在生长过程中颈部长度增加以及随后的重力性低血压刺激基础动脉血压升高时被激活。在人类和大鼠中，该机制通过供应脑干的动脉变窄而被激活。如果我们的观点正确，未来人类原发性高血压的成功治疗将包括降低脑动脉阻力的方法。
