Essential hypertension, accounting for greater than 90% of all hypertension, affects between 15 and 20% of all adults and is a significant risk factor for excess morbidity and mortality due to arteriosclerotic and cerebrovascular disease. Reduction of even mild hypertension has been shown to decrease long-term morbidity and mortality due to vascular disease. Excess sympathetic nervous system activity has been postulated as an etiologic factor in essential hypertension but direct measurement of circulating plasma norepinephrine and epinephrine levels as an indicator of sympathetic dysfunction has been equivocal. Direct studies of adrenergic receptor-effector mechanisms in essential hypertension have been scant but are suggestive of a generalized receptor-effector abnormality in hypertensive subjects. The present study is designed to study the effects of physical training, a modality known to reduce sympathetic activity, on adrenergic-receptor effector mechanisms and their relationship to blood pressure. Beta-2 and alpha-2 adrenergic receptors will be measured on circulating mononuclear leukocytes and platelets, respectively, in untreated hypertensive subjects (n=10) and matched normal controls (n=10) at baseline, after a one-month period with no therapy and after 12 weeks of bicycle ergometer exercise at 60% maximal oxygen consumption for 30 minutes, three times per week. Receptor studies will include standard saturation curves to measure apparent dissociation constant (Kd) and receptor density (Beta max). Beta-2 receptors will be measured with Iodocycopindolol-125, a Beta antagonist, an Alpha-2 receptors with [H-3]-UK-14304, an Alpha-2 agonist. In addition, competition studies will be done in the presence and absence of Gpp(NH)p to determine the percentage of receptors in high and low affinity binding states. Adenylate cyclase activity in response to isoproterenal stimulation (Beta-2) and epinephrine inhibition (Alpha-2) will also be done. It is expected that 1) hypertensive subjects will exhibit altered adrenergic receptor status when compared to normal controls that will correct after physical training and 2) correction of receptor abnormality will be correlated with a decrease in blood pressure.
