Effects of a new angiotensin-converting enzyme inhibitor, alacepril, on changes in neurohormonal factors and arterial baroreflex sensitivity in patients with congestive heart failure.
OBJECTIVE
Patients with heart failure have abnormal neurohormonal regulation during orthostatic stress, and abnormal arterial baroreflex function. This study investigated the effects of alacepril, a new angiotensin-converting enzyme inhibitor with sulfhydryls, on changes in neurohormonal factors during tilt and on the arterial baroreflex control of heart rate.


METHODS
Plasma concentrations of noradrenaline, adrenaline, renin activity, angiotensin II, and atrial natriuretic peptide were measured at supine rest and after 30 degrees head-up tilt with measurements of central venous pressure and cardiac dimensions in seven patients with congestive heart failure (65 years, ejection fraction = 34%). Arterial baroreflex control of heart rate was assessed by phenylephrine bolus. The arterial baroreflex test was re-examined 3 h after oral alacepril (37.5 mg). The tilt and arterial baroreflex tests were repeated 12 weeks after alacepril treatment (50 mg x day(-1)).


RESULTS
Heart rate, blood pressure, and neurohormonal factors did not differ before and after chronic alacepril, except for a trend toward an increase in renin activity (2.0 vs 4.9 ng x ml(-1) x h(-1)). Head-up tilt decreased central venous pressure (-2.5 mmHg) with a decrease in cardiac dimensions in the pre-alacepril phase. These changes were accompanied by increases in noradrenaline, adrenaline, and angiotensin II and a decrease in atrial natriuretic peptide. After chronic alacepril, the increase in noradrenaline during head-up tilt tended to be smaller (84 vs 30 pg x ml(-1)), with similar changes in central venous pressure (-3.4 mmHg) and cardiac dimensions. Both acute (3.6 vs 4.8 ms mmHg(-1)) and chronic (3.6 vs 6.7 ms mmHg(-1)) alacepril treatment was associated with a trend towards an increase in the arterial baroreflex control of heart rate.


CONCLUSIONS
These results suggest that treatment with alacepril may cause a reduction of sympathetic activation during orthostatic stress and may enhance arterial baroreflex function in patients with mild to moderate heart failure.
The 1st Department of Internal Medicine, Tottori University, Yonago, Japan. kinugawa@grape.med.tottori-u.ac.jp
T
T
Kinugawa
M
M
Kato
M
M
Mori
A
A
Endo
T
T
Kato
T
T
Hamada
N
N
Noguchi
H
H
Omodani
S
S
Osaki
K
K
Ogino
H
H
Miyakoda
I
I
Hisatome
C
C
Shigemasa
D000368:Aged; D000804:Angiotensin II / Q000097:blood / Q000187:drug effects; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000187:drug effects; D017704:Baroreflex / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000097:blood; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009479:Neuropeptides / Q000097:blood / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000097:blood*; D009638:Norepinephrine / Q000097:blood; D012083:Renin / Q000097:blood / Q000187:drug effects; D018667:Tilt-Table Test; D016277:Ventricular Function, Left / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D000804:Angiotensin II; D009320:Atrial Natriuretic Factor; D002216:Captopril; D012083:Renin; C046835:alacepril; D009638:Norepinephrine; D004837:Epinephrine