CARDIOVASCULAR AND ENDOCRINE PROFILE OF ADRENERGIC-NEURON BLOCKADE IN NORMAL AND HYPERTENSIVE MAN

Some cardiovascular and endocrine effects of adrenergic blockade were assessed in six normal subjects, six patients with mild hypertension (diastolic pressure < 100 mm Hg) and six patients with moderate to severe essential hypertension. Administration of the inhibitory agent, debrisoquine, for six weeks markedly decreased supine and upright plasma norepinephrine levels, and norepinephrine excretion in all three groups. Supine and upright blood pressure was decreased more (p < 0.001) in those with moderate to severe hypertension (15 and 27 per cent) than in those with mild hypertension (6 and 8 per cent) and remained unchanged in normal subjects. Pulse rate and plasma renin levels were lowered (p <0.01) in patients with moderate to severe hypertension, but not in normal or mildly hypertensive subjects. The different influence of blood pressure, pulse rate and renin in the three groups could not be explained by variations in drug dosage, norepinephrine inhibition, age, basal sodium balance or secondary blood volume expansion, the latter being marked in all groups. Diuretic therapy in addition to sympathetic inhibition reversed blood volume expansion, and further augmented the reduction in supine and upright blood pressure in patients with moderate to severe (-21 and -47 per cent) or mild hypertension (-8 and -12 per cent). Plasma aldosterone, cortisol and epinephrine values remained unchanged, and no severe or intolerable side effects occurred during treatment. These data suggest that adrenergic neuron blockade with modest doses of debrisoquine, combined with a diuretic, may be an effective and acceptable mode of therapy in patients with either mild or more severe hypertension. The hypotensive, cardiac-slowing and renin-inhibitory potential of adrenergic neuron blockade may be initiated by decreased norepinephrine outflow and modulated by variations in end-organ responsiveness, normal subjects being relatively insensitive and patients with essential hypertension being more sensitive as the severity of their hypertension increases. © 1978.