Pathophysiology of hypertension

Pathogenesis of hypertension: Primary hypertension has a multifactorial background, consisting of three main elements, (1) polygenic predisposition, (2) excitatory environmental effects and (3) structural upward resetting of the heart and vessels. These three elements are inter-related, since excitatory environmental effects are usually needed to precipitate the functional expression of genetic predisposition (particularly in man) and structural upward resetting is sometimes genetically facilitated. As hypertension progresses, the structural upward resetting becomes the dominating element, underlying the elevation in both pressure and resistance. Progression of hypertension: In the early phases of both human and animal models of primary hypertension, interactions between the genetic predisposition and excitatory environmental effects are often expressed mainly as mildly enhanced central neurohormonal activity. Not infrequently, cardiac output is increased more than systemic resistance. The structural factor, at this point, is still mainly expressed as a fairly reversible cardiac and vascular muscle hypertrophy (or hyperplasia), and a modest degree of resistance vascular narrowing. Aging effects on hypertension: The normal aging process affects the cardiovascular system to a greater degree in hypertensives than normotensives, implying more pronounced reductions in cardiac and vascular compliance, muscle strength and contractile speed, and in renal functional capacity. With age and a prolonged positive-feedback interaction between genetic/environmental factors and structural adaptation at the systemic resistance level, the structurally based elevation in resistance becomes even more dominant, and is further complicated by increasing interstitial involvement and therefore reduced reversibility. Thus, elderly hypertensives pose a great clinical challenge since they present treatment-resistant upward structural resetting, reduced cardiac and renal functional reserves, and reduced blood flow reserves in the important coronary, cerebral and renal circuits. The reduction in blood flow is due to vascular narrowing, a process which, in man, can be greatly aggravated by the presence of atherosclerosis. These principal events have been mainly illustrated by animal data, derived from comparisons of young and old spontaneously hypertensive and Wistar-Kyoto rats.