Angiotensin converting enzyme inhibition and sympathetic activity in healthy subjects

Background: One suggested mechanism for the reduction in mortality rates resulting from the use of angiotensin converting enzyme inhibitors in congestive heart failure is the inhibition of the angiotensin II-mediated norepinephrine release. Direct evidence for this mechanism is lacking in humans.

Subjects and Methods: We examined the effects of captopril, 25 mg three times a day, or matched placebo for 7 days on sympathetic activity during a 10 mEq/day sodium diet in seven healthy male subjects aged 30 ± 3 (SEM) years. A tritiated norepinephrine radioisotope dilution technique was used to measure sympathetic activity, both at rest and during isometric handgrip exercise.

Results: Captopril blunted the increase in mean arterial pressure during isometric handgrip exercise (placebo, from 81 ± 4 to 112 ± 2 mm Hg; captopril, from 78 ± 3 to 101 ± 2 mm Hg; p < 0.01). However, the increase in systemic norepinephrine spillover during isometric handgrip exercise was not blunted by captopril. Captopril had no effect on resting mean arterial pressure or systemic norepinephrine spillover.

Conclusions: Captopril did not attenuate baseline or static exercise-stimulated sympathetic activity in healthy subjects. These findings would indicate that angiotensin converting enzyme inhibition does not decrease sympathetic activity at rest or during the stimulus of isometric handgrip exercise.