Inhibition of the renin-angiotensin system ameliorates genetically determined hyperinsulinemia.
This study was performed in order to assess the potentially different effects of the angiotensin-converting enzyme inhibitor captopril and of the angiotensin II receptor antagonist irbesartan on the metabolic syndrome in an animal model. Male NZO/BL6 F1 mice were treated with captopril, irbesartan, or placebo for 10 months: Control animals treated with placebo developed a metabolic syndrome with obesity (55.5+/-6.3 g), hypertension (146+/-10 mm Hg), hyperinsulinemia (7.2+/-5.7 ng/ml), hypercholesterolemia (5.1+/-0.7 mmol/l), cardiac hypertrophy (269+/-44 mg) and atherosclerotic plaques in the ascending aorta (3.6+/-1.5 microm(2)). Treatment with angiotensin-converting enzyme inhibitor or angiotensin II receptor antagonist significantly (p<0.001) reduces hypertension (73+/-5 and 78+/-11 mm Hg), cardiac hypertrophy (203+/-26 and 202+/-18 mg) and atherosclerosis (2.2+/-0.9 and 1.8+/-0.8 microm(2)). In addition, they prevented the development of obesity (42.2+/-3.5 and 38.3+/-2.8 g) and hyperinsulinemia (3.6+/-1.5 and 1.8+/-0.4 ng/ml). In conclusion, long-term treatment with an angiotensin-converting enzyme inhibitor or an angiotensin II receptor antagonist can ameliorate obesity and hyperinsulinemia in a genetically determined mouse model.
Ortlepp
J R
JR
Medical Clinic I, University Hospital of Aachen, Pauwelsstrasse 30, 52057, Aachen, Germany. jort@pcserver.mk1.rwth-aachen.de
Breuer
J
J
Eitner
F
F
Kluge
K
K
Kluge
R
R
Floege
J
J
Hollweg
G
G
Hanrath
P
P
Joost
H G
HG
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001161:Arteriosclerosis / Q000517:prevention & control; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D006332:Cardiomegaly / Q000517:prevention & control; D005260:Female; D006946:Hyperinsulinism / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control*; D006973:Hypertension / Q000517:prevention & control; D000077405:Irbesartan; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology*; D013997:Time Factors
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D013777:Tetrazoles; D002216:Captopril; D000077405:Irbesartan