The effects of ramipril on sympathetic nervous system function in older patients with hypertension

Background: There are important interactions between the renin-angiotensin system and the sympathetic nervous system, Therapy with angiotensin-convert ing enzyme (ACE) inhibitors may suppress sympathetic nervous system activit y. Objective: To test the hypothesis that long-term ACE inhibition by ramipril will suppress sympathetic nervous system activity and up-regulate a-adrene rgic receptor responsiveness in older patients with hypertension, Methods: This placebo-controlled, double-blind randomized study was conduct ed at the University Hospital, General Clinical Research Center, University of Michigan Medical Center, Fifteen healthy older patients with mild to mo derate hypertension received 8 weeks of ramipril therapy with doses ranging from 5 mg to 20 mg, The following measurements were obtained: plasma norep inephrine levels; norepinephrine kinetic parameters derived from plasma nor epinephrine and H-3-norepinephrine levels obtained during infusion and disa ppearance of H-3-norepinephrine, including the extravascular norepinephrine release rate, norepinephrine clearance, spillover fraction, and volume of distribution; forearm blood flow; platelet membrane alpha(2)-receptor bindi ng characteristics, and adenylyl cyclase activity. Results: Although plasma norepinephrine levels increased in the subjects tr eated with ramipril, there were no significant differences from baseline in the rate of norepinephrine appearance into the vascular compartment (P = . 76) or in the rate of norepinephrine release into the extravascular compart ment (P = .92), In addition, no differences were observed in other norepine phrine kinetic parameters (norepinephrine spillover fraction, norepinephrin e volume of distribution, or clearance) between the ramipril and placebo gr oups, Consistent with this, then was no apparent change in measures of vasc ular or platelet alpha-adrenergic receptor responsiveness. Conclusions: Ramipril therapy did not suppress systemic sympathetic nervous system activity, alter other norepinephrine kinetic parameters, or alter a lpha-adrenergic responsiveness in older patients with hypertension.