Overexpression of endothelial nitric oxide synthase attenuates cardiac hypertrophy induced by chronic isoproterenol infusion.
Endogenous nitric oxide (NO) inhibits the contractile response to beta-adrenergic stimulation, but its effect on cardiac hypertrophy mediated by beta-adrenoceptors remains unclear. The present study was designed to determine whether overproduction of endothelial NO synthase (eNOS) could inhibit cardiac hypertrophy induced by chronic isoproterenol (ISO) infusion (30mg/kg per day) using eNOS overexpressing (eNOS-Tg) mice and wild-type (WT) mice. In a separate group, WT mice were treated with ISO and hydralazine to decrease blood pressure to the same levels in eNOS-Tg mice. The eNOS expression, NOS activity, and cGMP levels in the heart were remarkably higher in eNOS-Tg mice than in WT mice. ISO increased both heart weight and the heart/body weight ratio, which were significantly attenuated in eNOS-Tg mice compared with WT or hydralazine-treated WT mice. Histological examination revealed that the extent of fibrosis was not significantly different among the 3 groups, and that the increase in myocyte size was more than 10% lower in eNOS-Tg than in the other groups. In addition, up-regulated expression of atrial natriuretic peptide mRNA associated with cardiac hypertrophy was significantly inhibited in eNOS-Tg mice during ISO infusion. These results indicate that endogenous NO might act as a negative modulator for the hypertrophic response to beta-adrenergic stimulation.
Ozaki
Masanori
M
Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan.
Kawashima
Seinosuke
S
Yamashita
Tomoya
T
Hirase
Tetsuaki
T
Ohashi
Yoshitaka
Y
Inoue
Nobutaka
N
Hirata
Ken-ichi
K
Yokoyama
Mitsuhiro
M
D000318:Adrenergic beta-Agonists / Q000009:adverse effects*; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D007545:Isoproterenol; D051379:Mice; D008822:Mice, Transgenic; D032342:Muscle Cells / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D019001:Nitric Oxide Synthase; D007545:Isoproterenol