Folkow B
Department of Physiology, University of Göteborg, Sweden.
Hypertension. 1990 Jul;16(1):89-101. doi: 10.1161/01.hyp.16.1.89.
The history of research on the "structural factor" in primary hypertension is briefly reviewed, and the gradual realization of its important influence on the hemodynamics of hypertension is outlined, as seen from a "personal angle." Experiences from previous studies of normal vascular function in animals were decisive for our first hemodynamic demonstration concerning the "structural upward resetting" of the systemic resistance vessels in human primary hypertension. Subsequent quantitative studies in rats with primary and secondary hypertension complemented these studies, confirming that the critical structural changes are a rapid increase in precapillary resistance at full dilatation associated with an increase in wall/lumen ratio due mainly to media hypertrophy and occurring in both primary and renal hypertension. Analyses were also performed concerning cardiac, barostat, and venous structural resettings, which are briefly mentioned. In our first studies of human primary hypertension, we suggested that the structural factor might itself be genetically reinforced, and increasing evidence in favor of this view is now accumulating. It is further discussed how antihypertensive therapy should be directed primarily against the structural upward resetting, as dependent on the local pressure and "trophic" influences, and some of our results in rat models are outlined. Finally, as the structural factor at the systemic resistance level also invites positive feedback interactions with functional "pressor" influences, it is, in a way, more difficult to explain why 85-90% of people remain normotensive than how hypertension gradually develops in 10-15% of people. This points to some powerful and durable negative feedbacks, which are still poorly understood, because most so far known barostats are readily reset upward in hypertension. It is here that the Muirhead renomedullary depressor system, and perhaps also the unmyelinated baroreceptor-volume receptor afferents, may be of particular importance.
本文简要回顾了原发性高血压“结构因素”的研究历史,并从“个人视角”概述了人们逐渐认识到其对高血压血流动力学的重要影响。以往对动物正常血管功能的研究经验,对我们首次关于人类原发性高血压全身阻力血管“结构上调重置”的血流动力学论证起了决定性作用。随后对原发性和继发性高血压大鼠的定量研究补充了这些研究,证实关键的结构变化是在完全扩张时毛细血管前阻力迅速增加,同时壁/腔比值增加,主要是由于中膜肥厚,原发性高血压和肾性高血压均会出现这种情况。还对心脏、压力感受器和静脉结构重置进行了分析,并简要提及。在我们对人类原发性高血压的首次研究中,我们提出结构因素本身可能受基因强化,目前支持这一观点的证据越来越多。进一步讨论了抗高血压治疗应如何主要针对结构上调重置,这取决于局部压力和“营养”影响,并概述了我们在大鼠模型中的一些结果。最后,由于全身阻力水平的结构因素也会引发与功能性“升压”影响的正反馈相互作用,从某种程度上说,解释为什么85 - 90%的人血压正常比解释10 - 15%的人如何逐渐发展为高血压更困难。这表明存在一些强大而持久的负反馈,目前仍知之甚少,因为迄今为止已知的大多数压力感受器在高血压中很容易向上重置。在这里,缪尔黑德肾髓质降压系统,也许还有无髓压力感受器 - 容量感受器传入神经,可能特别重要。