Does lipophilicity of angiotensin converting enzyme inhibitors selectively influence autonomic neural function in human hypertension?
BACKGROUND
Angiotensin II has both central nervous system and peripheral effects on autonomic function. Ramipril is among the more lipophilic angiotensin converting enzyme (ACE) inhibitors, and hence can penetrate the central nervous system readily.


METHODS
We investigated whether rampiril has selective effects on autonomic control of the circulation in human hypertension, compared with the more hydrophilic ACE inhibitor enalapril. Blood pressure, hemodynamics and measurements of autonomic function were obtained in 13 essential hypertensive subjects after 10 days on placebo, and after crossover monotherapy with 10 days on enalapril versus 10 days on ramipril.


RESULTS
Both enalapril and ramipril lowered systolic, diastolic and mean arterial blood pressures significantly, with no reflex increase in heart rate. Plasma renin activity increased substantially on each of the ACE inhibitors. There were no significant effects of either agent on plasma catecholamines (norepinephrine or epinephrine) or chromogranin A, biochemical indices of efferent sympatho-adrenal outflow. There were also no significant changes after either agent in baroreflex sensitivity (to high- and low-pressure stimuli), the response to cold stress or sympathetic (alpha-adrenergic) participation in blood pressure maintenance. There was a marginal effect of ACE inhibition on alpha 1-adrenergic pressor sensitivity, but the two compounds did not differ significantly in this respect.


CONCLUSIONS
Autonomic control of circulatory function was maintained well after either lipophilic (ramipril) or hydrophilic (enalapril) ACE inhibitors, and the lipophilic compound ramipril had no additional effects on autonomic function beyond those shown by the hydrophilic agent enalapril.
Wu
R A
RA
Department of Medicine, University of California, San Diego 92161.
Kailasam
M T
MT
Cervenka
J H
JH
Parmer
R J
RJ
Kennedy
B P
BP
Ziegler
M G
MG
O'Connor
D T
DT
D000450:Aldosterone / Q000097:blood; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D003080:Cold Temperature; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004656:Enalapril / Q000627:therapeutic use*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D017257:Ramipril / Q000627:therapeutic use*; D012083:Renin / Q000097:blood
D002395:Catecholamines; D000450:Aldosterone; D004656:Enalapril; D012083:Renin; D017257:Ramipril