Hemodynamic and neurohumoral evidence of multifaceted pathophysiology in human hypertension

Abstract

As hypertension advances, secondary pathophysiologic changes are induced in multiple organs. Consequently, we investigated the pathophysiology of the earliest forms of hypertension--e.g., borderline hypertension. Borderline hypertension is associated with abnormal autonomic control of the circulation; sympathetic drive to the heart, blood vessels, and kidney is increased, cardiac parasympathetic inhibition is decreased, and plasma norepinephrine is increased. The hemodynamic picture is one of increased cardiac output not met by adequate vasodilation. The condition of "hyperkinetic" borderline hypertension is a precursor of more severe hypertension. In due course, a transition from high cardiac output to high vascular resistance occurs, while the enhanced sympathetic tone recedes toward normal values. The mechanism of hemodynamic transition is easily understood: cardiac output decreases due to structural changes and receptor downregulation, whereas ensuing vascular hypertrophy increases vascular resistance. The apparent regression of plasma norepinephrine values is explained in the framework of our hypothesis of the "blood pressure-seeking properties of the central nervous system." Large body mass and overweight are a consistent feature of borderline hypertension. A recent study in Tecumseh, Michigan shows that weight, plasma norepinephrine, a hyperkinetic state, and plasma insulin values are correlated in the general population. The explanation of this interrelationship will greatly advance our understanding of hypertension. From the pathophysiological viewpoint, the paradoxical outcome of clinical trials involving older antihypertensive medication is not surprising. The complexity of pathophysiologic interrelationships and the fact that risk factors for atherosclerosis are increased in hypertension suggest that reduction of blood pressure cannot be expected to ameliorate all consequences of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)