Poor regression of myocardial hypertrophy following concomitant chronic alcohol ingestion and angiotensin converting enzyme (ACE) inhibition.
In the following study we examined the combined effect of chronic alcohol administration and anti-hypertensive drug treatment in spontaneously hypertensive rats (SHR). SHR were fed alcohol for six weeks while taking the angiotensin converting enzyme (ACE) inhibitor lisinopril. After six weeks, protein synthesis rates, contractile protein levels and protease activities were examined in control; alcohol; control+lisinopril; alcohol+lisinopril groups. Lisinopril treatment significantly reduced left ventricular mass, protein content and contractile proteins in control rats, but these effects were not as pronounced in alcohol+lisinopril rats. Protein synthesis rates in both mixed and myofibrillar fractions were not significantly different in any of the 4 groups. The enzyme activities of the proteases cathepsin D and dipeptidyl aminopepetidase I increased in control+lisinopril rats, however, this effect was not evident in alcohol+lisinopril rats. Contractile proteins identified by one-dimensional electrophoresis showed that lisinopril treatment reduced all contractile proteins in control rats. However, in alcohol+ lisinopril rats, myosin heavy chain was higher than in control+lisinopril rats. In summary, alcohol ingestion impairs the regression of the hypertrophic myocardium in SHR on ACE-inhibitor treatment, which was reflected by altered protein metabolism. This study suggests that successful anti-hypertensive treatment may not be achieved if alcohol misuse is evident.
Patel
V B
VB
Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Sandhu
G
G
Dunn
M J
MJ
Mantle
D
D
Rodrigues
L M
LM
Griffiths
J R
JR
Wassif
W
W
Richardson
P J
PJ
Preedy
V R
VR
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D002312:Cardiomyopathy, Hypertrophic / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002492:Central Nervous System Depressants / Q000008:administration & dosage*; D004347:Drug Interactions; D000431:Ethanol / Q000008:administration & dosage*; D017706:Lisinopril / Q000008:administration & dosage*; D009124:Muscle Proteins / Q000096:biosynthesis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000806:Angiotensin-Converting Enzyme Inhibitors; D002492:Central Nervous System Depressants; D009124:Muscle Proteins; D000431:Ethanol; D017706:Lisinopril