Comparative effects of type 1 angiotensin II-receptor blockade with angiotensin-converting-enzyme inhibitor on left ventricular distensibility and collagen metabolism in spontaneously hypertensive rats.
We compared the cardiac effects of the selective angiotensin II type 1 (AT1)-receptor blockade, FK-739, with an angiotensin-converting-enzyme (ACE) inhibitor, enalapril, on left ventricular (LV) distensibility and collagen metabolism in spontaneously hypertensive rats (SHRs). We treated 14-week-old SHRs with FK-739 (30 mg/kg/day) or enalapril (10 mg/kg/day) for 6 weeks. Both FK-739 and enalapril induced a significant decrease in blood pressure (p < 0.001) and regression of LV hypertrophy (p < 0.001) compared with vehicle, with no differences between the treated groups. Furthermore, FK-739 caused a greater decrease in LV collagen content than did enalapril (FK-739-treated group, 3.06 +/- 0.11 mg/g; enalapril-treated group, 3.47 +/- 0.05 mg/g; p = 0.015) with no change in collagen phenotypes. Hearts taken from rats treated with FK-739 also showed greater LV distensibility than those taken from enalapril-treated rats (FK-739-treated group vs. enalapril-treated group at > or = 15 mm Hg, p < 0.001). These results suggest that, compared with ACE inhibition, AT1-receptor blockade may have additional effects on LV distensibility and collagen metabolism in the regression of LV hypertrophy induced by pressure overload.
Yonezawa
T
T
2nd Department of Internal Medicine, Yamaguchi University School of Medicine, Japan.
Umemoto
S
S
Fujii
A
A
Katayama
K
K
Matsuzaki
M
M
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D003094:Collagen / Q000378:metabolism*; D004656:Enalapril / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000737:chemistry / Q000187:drug effects; D006909:Hydroxyproline / Q000096:biosynthesis; D017379:Hypertrophy, Left Ventricular / Q000473:pathology / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR
C085920:2-butyl-3-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-3H-imidazo(4,5-b)pyridine; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D004656:Enalapril; D003094:Collagen; D006909:Hydroxyproline