Studies of the Mechanisms Underlying Impairment of Beta-Adrenoceptor-Mediated Effects in Human Hypertension

SUMMARY To investigate the impairment of beta-adrenoceptor responsiveness in human hyper-tension, we evaluated the effect of an oral salt load (400 mEq/day of NaCI for 7 days) on plasma catecholamine concentrations and beta-adrenoceptor-mediated effects in 11 young patients with mild essential hypertension. Responses of heart rate and plasma cAMP to isoproterenol administration were used as indices of beta-adrenoceptor responsiveness. Salt loading induced a significant reduction in the dose of isoproterenol required to raise the heart rate by 25 bpm (CD2S) (from 7.6 ± 1.5 to 5.3 ± 0.9 /xg, p < 0.05) and an increase in the slopes of the regression lines for heart rate changes and isoproterenol doses (AHR/IS) (from 3.3 ± 0.6 to 4.7 ± 0.7, p < 0.05) and for plasma cyclic AMP (cAMP) level changes and isoproterenol doses (AcAMP/IS) (from 0.3 ± 0.06 to 1.4 ± 0.3, p < 0.05). After salt loading there was a significant reduction in plasma catecholamine concentrations with a significant relationship between changes in upright plasma epinephrine levels and changes in CD25 (r = 0.904, p < 0.01) and in the slopes for AHR/IS (r = 0.983, p < 0.001) and AcAMP/IS (r = 0.922, p < 0.001). These results support the hypothesis that the impairment of beta-adrenoceptor sensitivity observed in human hypertension is associated with a beta-adrenoceptor overstimulation due to chronically elevated adrenergic tone. (Hypertension 5: 584-590, 1983