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

• Published in: Clinical pharmacology and therapeutics 1999-04, Vol.65 (4), p.420-427
• Main Authors: Lee, Cathy C., Sidani, Mohamad A., Hogikyan, Robert V., Supiano, Mark A.
• Format: Article
• Language: English
• Subjects: Aged; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Antihypertensive agents; Antihypertensive Agents - pharmacology; Antihypertensive Agents - therapeutic use; Biological and medical sciences; Blood Flow Velocity - drug effects; Blood Platelets - metabolism; Cardiovascular system; Cell Membrane - metabolism; Double-Blind Method; Female; Forearm - blood supply; Humans; Hypertension - drug therapy; Hypertension - physiopathology; Male; Medical sciences; Middle Aged; Norepinephrine - blood; Pharmacology. Drug treatments; Ramipril - pharmacology; Ramipril - therapeutic use; Receptors, Adrenergic, alpha - drug effects
• ISSN: 0009-9236; 1532-6535
• DOI: 10.1016/S0009-9236(99)70137-2

Background There are important interactions between the renin‐angiotensin system and the sympathetic nervous system. Therapy with angiotensin‐converting enzyme (ACE) inhibitors may suppress sympathetic nervous system activity. Objective To test the hypothesis that long‐term ACE inhibition by ramipril will suppress sympathetic nervous system activity and up‐regulate α‐adrenergic receptor responsiveness in older patients with hypertension. Methods This placebo‐controlled, double‐blind randomized study was conducted at the University Hospital, General Clinical Research Center, University of Michigan Medical Center. Fifteen healthy older patients with mild to moderate hypertension received 8 weeks of ramipril therapy with doses ranging from 5 mg to 20 mg. The following measurements were obtained: plasma norepinephrine levels; norepinephrine kinetic parameters derived from plasma norepinephrine and 3H‐norepinephrine levels obtained during infusion and disappearance of 3H‐norepinephrine, including the extravascular norepinephrine release rate, norepinephrine clearance, spillover fraction, and volume of distribution; forearm blood flow; platelet membrane α2‐receptor binding characteristics, and adenylyl cyclase activity. Results Although plasma norepinephrine levels increased in the subjects treated 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 compartment (P = .92). In addition, no differences were observed in other norepinephrine kinetic parameters (norepinephrine spillover fraction, norepinephrine volume of distribution, or clearance) between the ramipril and placebo groups. Consistent with this, there was no apparent change in measures of vascular or platelet α‐adrenergic receptor responsiveness. Conclusions Ramipril therapy did not suppress systemic sympathetic nervous system activity, alter other norepinephrine kinetic parameters, or alter α‐adrenergic responsiveness in older patients with hypertension. Clinical Pharmacology & Therapeutics (1999) 65, 420–427; doi: