SYMPATHETIC OVERACTIVITY AND CORONARY RISK IN HYPERTENSION

Abstract

Tecumseh, Michigan. Nearly one thousand subjects were enrolled into the study and anthropometric, hemodynamic and metabolic data were collected at several time points. When first examined as children those subjects who were ultimately to develop borderline hypertension had significantly faster heart rates than their future normotensive counterparts despite having comparable blood pressures as children.( 1) As they aged the difference between the pulse rate was maintained and the blood pressure in the borderline hypertensive group had become elevated. When examined as adults (1 8-42 years) the differences in pulse rate and blood pressure persisted between the groups and elevated plasma noradrenaline was demonstrated in the hyperkinetic (high cardiac output, increased heart rate) hypertensive subjects. An significant increase in cardiac risk factors was found in the hypertensive group as a whole and also in the subpopulation of pure hyperkinetic hypertensive subjects (2) and a strong correlation between diastolic blood pressure and these risk factors was also found (3). This data suggests that there was a relative overactivity of the sympathetic nervous system present from an early age in the subjects who were to develop borderline hypertension and that this persisted into at least early adulthood. It also raises the intriguing possibility that sympathetic excess could not only be responsible for the blood pressure elevation in these subjects but also independently result in the increase in coronary risk factors. A hypothetical schema for just such an association will be described where excess sympathetic tone is the underlying pathophysiological state that leads to an increased tendency to atherosclerosis and insulin resistance as well as a propensity to coronary thrombosis, coronary spasm and arrhythmia's. Insulin resistance has been shown to be associated with hypertension (4) and is accompanied by an increased coronary morbidity (5). Excess sympathetic tone may produce insulin resistance by promoting a-adrenergic vasoconstriction and reducing the delivery of insulin and glucose to skeletal muscle, which is thought to be the site of insulin resistance in hypertension. Jamerson 's work (6) lends support to this concept when it was demonstrated that decreased blood flow in the human forearm produced by reflex activation of the sympathetic nervous system results in decreased glucose utilization, a condition analogous to insulin resistance. This type of sympathetically mediated insulin resistance may be compounded by the trophic effects of elevated insulin on the vascular wall (7) and by vascular rarefaction which has been documented to occur in hypertension (8). Further evidence for a role of the sympathetic nervous system in altered insulin sensitivity in