Norepinephrine clearance and pressor effect in normal and hypertensive man.

Abstract

Whether and to what extent the sympathetic nervous system participates in the development of essential hypertension has remained largely unclear. The role of the adrenergic effector - cardiovascular response axis in the pathogenesis of essential hypertension was investigated by combined analysis of blood levels, total plasma clearance and cardiovascular pressor effects of norepinephrine (NE). Measurements of plasma NE and blood pressure were performed before, during and after an intravenous infusion of NE at stepwise increasing rates in approximately age and sex-matched groups of 28 normal subjects and 35 patients with essential hypertension. The threshold of the pressor effect of NE was lower in hypertensive than in normal subjects (20 +/- 10 vs. 42 +/- 26 ng/kg min; P < 0.001); but the slope of the dose - resonse curve and basal endogenous plasma NE were in the average similar. Total plasma NE clearance estimated under steady state conditions was similar in normal and hypertensive subjects (5.3 +/- 2.5 vs. 5.4 +/- 2.31/min). NE clearance corrleated inversely with basal plasma NE in normal subjects (r = 0.57; P < 0.005). The plasma half-life of NE was about 2 min. These findings demonstrate that basal blood levels and total plasma clearance of NE during NE infusion are usually normal in essential hypertension. A low threshold of the pressor effect of NE in the presence of normal adrenergic activity may contribute to the development and/or maintenance of essential hypertension.