Cardiovascular Pressor Reactivity as Related to Plasma Catecholamines: Role in the Pathogenesis of Essential Hypertension and in the Antihypertensive Mechanism of Diuretic Treatment

Abstract

The role of the adrenergic effector-response axis in the pathogenesis of essential hypertension and in the hypotensive mechanism of diuretic treatment was evaluated by combined analysis of plasma catecholamine levels and pressor sensitivity to norepinephrine (NE).

Under placebo conditions, plasma NE, epinephrine and dopamine concentrations did not differ significantly between normal subjects and patients with borderline or established essential hypertension. The pressor dose (Δ mean blood pressure + 20 mm Hg) of infused NE correlated positively (P < 0.05) with endogenous plasma NE; however, this relationship was shifted in hypertensive patients so that NE pressor dose at any basal plasma NE level tended to be decreased. Compared to normal subjects, NE pressor dose was decreased. Compared to normal subjects, NE pressor dose was decreased slightly (P < 0.01) in borderline and markedly (P < 0.001) in established hypertension; it correlated inversely (P < 0.01) with basal blood pressure.

Adrenergic neuronal blockage with debrisoquine decreased plasma NE by 50% in all three groups; blood pressure remained largely unchanged in normal subjects, decreased only slightly (-5%) in borderline and fell significantly more in established hypertension (-21%). Thus, the ratio between debrisoquine-induced changes in blood pressure and plasma NE was greater (P < 0.001) in established hypertension than in normal or borderline hypertensive subjects.

Following six weeks of treatment with thiazidelike diuretics, basal plasma catecholamines, NE pressor dose and blood pressure remained unchanged in normal subjects. In hypertensive patients, diuretics caused a reduction (P < 0.01) in blood pressure and NE pressor reactivity, while basal plasma catecholamine levels were not significantly changed. Diuretic-induced changes in blood pressure and NE pressor dose were correlated (R = 0.40; P < 0.05).

These findings suggest that increased cardiovascular reactivity to NE occurs already at the borderline stage of hypertension. Borderline or established essential hypertension may be maintained, at least in part, by the inappropriate association of normal adrenergic activity with increased NE pressor reactivity. Diuretics may decrease blood pressure in essential hypertension by reducing an inappropriately high NE pressor reactivity without causing a concomitant equivalent increase in adrenergic nervous activity.

A modified version of this paper has been presented at the Symposium of the Swiss Association against High blood pressure, June 1979, Glion, Switzerland. Therefore, it appeared with slight modifications also as a part of the proceedings of the Glion Symposium in Clin. Exp. Hypertension, 1979