Short-term systemic hemodynamic adaptation to beta-adrenergic inhibition with atenolol in hypertensive patients

Early systemic hemodynamic adjustments to antihypertensive therapy with the cardioselective beta inhibitor, atenolol, were investigated in 12 hospitalized men, mean age 52 years, with uncomplicated mild-to-moderate essential hypertension. Twice daily measurements of cardiac output (CO) by CO2 rebreathing, blood pressure by cuff, and heart rate were performed in all subjects for 3 days before and 5 days after initiation of oral atenolol therapy (50 or 100 mg daily). Cardiac output by CO2 rebreathing was checked with dye dilution just before, and 4 hours and 4 days after the start of therapy. Plasma volume (radioiodinated albumin) was measured before therapy and on Day 5 of therapy. The CO results obtained with the two methods were not significantly different (r = 0.88, p less than 0.01, n = 12). A reduction in heart rate, 18 +/- 2 beats/min (mean +/- SE), occurred in all patients while taking atenolol. By 4 hours after the first dose of atenolol, CO fell from 5.49 +/- 0./30 to 4.24 +/- 0.21 liters/min (p less than 0.01), while the control mean arterial pressure (MAP) of 108 +/- 4 mm Hg was not significantly changed, 110 +/- 4 mm Hg. At 24 hours, CO returned near baseline (5.10 +/- 0.21 liters/min) but MAP was reduced (95 +/- 3 mm Hg, p less than 0.001) and remained so thereafter. CO remained at baseline at 48 hours (5.50 +/- 0.29 liters/min) but fell again (p less than 0.01) to 4.81 +/- 0.11 on Day 4 and to 4.68 +/- 0.25 liters/min on Day 5 of atenolol therapy. Plasma volume, 3110 +/- 100 ml before therapy, was reduced to 2850 +/- 100 by Day 5 of atenolol therapy (p less than 0.01). The findings indicate a delayed onset of the antihypertensive action of atenolol. The transient return to baseline of CO on Day 2 and 3 of atenolol therapy suggests a reverse autoregulatory adjustment to the initial fall in CO.