Differential Modulation of Baroreceptor Sensitivity by Long-term Antihypertensive Treatment

Abstract

Abstract We investigated the effects of long-term oral treatment with four different classes of antihypertensive drugs (a thiazide diuretic [trichlormethiazide, 10 mg/kg per day]; a β-blocker [atenolol, 90 mg/kg per day]; a calcium channel antagonist [nicardipine, 150 mg/kg per day]; and an angiotensin-converting enzyme inhibitor [enalapril maleate, 10 mg/kg per day]) on aortic baroreceptor activity in spontaneously hypertensive rats with chronic hypertension (36 weeks of age). Treatment with each of the four drugs, given from 10 to 36 weeks of age, similarly decreased arterial pressure (171±2 to 144±1 mm Hg, P <.01) and similarly decreased the threshold pressure for baroreceptors (116±3 to 103±1 mm Hg, P <.05). The four antihypertensive drugs also potentiated the maximal gain of the pressure-activity relation in these rats (untreated, 1.08±0.05% maximum/mm Hg); however, nicardipine and enalapril (1.77±0.04% and 1.70±0.06% maximum/mm Hg, respectively) augmented the maximal gain to a greater extent (P <.05 to .01) than did trichlormethiazide or atenolol (1.49±0.05% and 1.42±0.02% maximum/mm Hg, respectively). When the initiation of treatment was delayed to 28 weeks of age, no differences were found in the effects on either threshold pressure (104±1 mm Hg) or maximal gain (1.36±0.03% maximum/mm Hg) for all four drugs. These findings suggest that in the treatment of chronic hypertension (1) baroreceptor resetting to a lower pressure level is similarly induced with the four drugs, and (2) baroreceptor sensitivity is augmented more by early and long-term treatment with calcium channel antagonists or angiotensin-converting enzyme inhibitors than by diuretics or β-blockers.