2-Tetradecylglycidic acid, an inhibitor of carnitine palmitoyltransferase-1, induces myocardial hypertrophy via the AT1 receptor.
Activation of the antiogensin II, type 1 (AT1) receptor mediates the myocardial response to numerous hypertrophic stimuli. This study tested the hypothesis that 2-tetradecylglycidic acid (TDGA), an oxirane carboxylate inhibitor of mitochondrial carnitine plamitoyltransferase-1, induces myocardial hypertrophy via the AT1 receptor system. Male Sprague-Dawley rats treated with 10 mg TDGA/kg/day for 7 days had a heart wet weight:body weight ratio of 3. 58+/-0.16 mg/g compared with a ratio of 2.79+/-0.07 for rats treated with vehicle (P<0.05). The plasma level of antiogensin II was 117. 75+/-17.39 pg/ml in rats treated with 10 mg TDGA/kg/day compared with 54.0+/-11.38 pg/ml for rats treated with vehicle (P<0.05). The plasma level of angiotensin I in these two groups of rats was not different statistically. Rats treated with TDGA and given drinking water containing 1 mg losartan/ml had a heart wet weight:body weight ratio of 2.84+/-0.05 mg/g. This value was not statistically different from the value measured in rats given drinking water containing 1 mg losartan/ml and treated with vehicle alone. No significant difference in the heart wet weight:dry weight ratio occurred among these groups of rats. Finally, treating rats with TDGA or giving rats drinking water that contained 1 mg losartan/ml altered neither their heart rate nor their mean arterial blood pressure when compared with untreated rats. This data, therefore, suggests that oxirane carboxylates induce myocardial hypertrophy by activating the AT1 receptor independent of changes in systemic hemodynamics.
Wolkowicz
P E
PE
The Center for NMR Research and Development, University of Alabama at Birmingham, Birmingham, Alabama, 35294, USA.
Urthaler
F
F
Forrest
C
C
Shen
H
H
Durand
J
J
Wei
C C
CC
Oparil
S
S
Dell'Italia
L J
LJ
D000818:Animals; D001835:Body Weight; D006332:Cardiomegaly / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004852:Epoxy Compounds / Q000008:administration & dosage*; D005227:Fatty Acids / Q000008:administration & dosage*; D006339:Heart Rate; D006439:Hemodynamics; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000502:physiology*
D004852:Epoxy Compounds; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D002334:Carnitine O-Palmitoyltransferase; C021756:2-tetradecylglycidic acid