Personal and Historical Perspectives in Hypertension "Structural Factor" in Primary and Secondary Hypertension

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. {Hypertension 1990;16:89-101)