DuP 753 Is More Effective Than Captopril on Baroreceptor Function in High-Renin Hypertension

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Abstract

High-renin hypertensive rats exhibit a general impairment of the baroreceptor reflexes. In the present study we compared the effect of the angiotensin converting enzyme inhibitor captopril (10 mg/kg per day) with the effect of the selective angiotensin subtype 1 receptor blocker DuP 753 (10 mg/kg per day) on the baroreceptor reflex bradycardia (progressive doses of phenylephrine) and baroreceptor reflex tachycardia (progressive doses of nitroprusside) in conscious rats 7 days after aortic ligation. Arterial pressure was markedly reduced after both acute (15-minute) treatment with captopril (123±6 versus 184±23 mm Hg) and DuP 753 (140±10.5 versus 181±5.4 mm Hg), but the depressed baroreceptor reflex bradycardia increased only after DuP 753 (1.13±0.22 versus 0.75±0.60 beats per minute [bpm]/mm Hg) and remained attenuated after captopril (0.54±0.086 versus 0.30±0.07 bpm/ mm Hg). After a 2-day treatment, captopril reduced arterial pressure (95±5 versus 184±2.3 mm Hg) to lower levels than DuP 753 (119±6 versus 172±4.6 mm Hg), whereas the depressed baroreceptor reflex bradycardia remained unchanged with captopril (0.46±0.13 versus 0.31±0.076 bpm/mm Hg) and increased with DuP 753 (1.13±0.19 versus 0.38±0.12 bpm/ mm Hg). Neither DuP 753 nor captopril administered acutely (15 minutes) or for 2 days significantly altered the depressed baroreceptor reflex tachycardia. We conclude (1) that DuP 753 was more efficient than captopril in the reversal of the depressed baroreceptor reflex sensitivity for bradycardic responses of rats with high-renin hypertension even when the reversal of hypertension was similar, and (2) that within the first 2 days, neither DuP 753 nor captopril significantly reverted the depressed baroreceptor reflex tachycardia.

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