Effect of losartan, an AT1 selective angiotensin II receptor antagonist, on isoproterenol-induced cardiac ornithine decarboxylase activity.
Ornithine decarboxylase (ODC,EC 4.1.1.7), a rate-limiting enzyme in polyamine biosynthesis, is known to be induced by a beta-adrenoceptor agonist, isoproterenol (ISO). ODC activity and cardiac polyamine content are considered to be correlated with ISO-induced cardiac hypertrophy in rat hearts. To determine whether ISO-induced cardiac ODC activity is mediated through the renin-angiotensin system, especially at the AT1-receptor, we used a nonpeptide AT1 receptor antagonist, losartan, in this study. Losartan (10 mg/kg) suppressed both heart ODC and polyamine contents in ISO-treated rats. Although metoprolol (a selective beta-adrenoceptor antagonist) totally suppressed ODC activity, these results suggest that ISO-stimulated cardiac ODC activity may be regulated through beta 2-adrenoceptors coupled with AT1 receptors in rats.
Nakano
M
M
Second Department of Internal Medicine, Gunma University School of Medicine, Japan.
Kanda
T
T
Matsuzaki
S
S
Hasegawa
S
S
Ma
H
H
Imai
S
S
Suzuki
T
T
Kobayashi
I
I
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D019808:Losartan; D008790:Metoprolol / Q000494:pharmacology; D009206:Myocardium / Q000201:enzymology*; D009392:Nephrectomy; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D065108:Ornithine Decarboxylase Inhibitors; D011700:Putrescine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D065108:Ornithine Decarboxylase Inhibitors; D013777:Tetrazoles; D000804:Angiotensin II; D009955:Ornithine Decarboxylase; D008790:Metoprolol; D019808:Losartan; D007545:Isoproterenol; D011700:Putrescine