Deficiency of iNOS Does Not Prevent Isoproterenol-induced Cardiac Hypertrophy in Mice.
10.4196/kjpp.2009.13.3.153
- Author:
Hye Na CHA
1
;
Geu Ru HONG
;
Yong Woon KIM
;
Jong Yeon KIM
;
Jin Myoung DAN
;
So Young PARK
Author Information
1. Department of Physiology, College of Medicine, Yeungnam University, Daegu 705-717, Korea. sypark@med.yu.ac.kr
- Publication Type:Original Article
- Keywords:
Inducible nitric oxide synthase;
Isoproterenol;
Cardiac hypertrophy
- MeSH:
Animals;
Body Weight;
Cardiomegaly;
Extracellular Signal-Regulated MAP Kinases;
Gene Expression;
Heart;
Heart Ventricles;
Interleukin-6;
Isoproterenol;
Mice;
Nitric Oxide Synthase Type II;
RNA, Messenger;
Transforming Growth Factor beta
- From:The Korean Journal of Physiology and Pharmacology
2009;13(3):153-159
- CountryRepublic of Korea
- Language:English
-
Abstract:
We investigated whether deficiency of inducible nitric oxide synthase (iNOS) could prevent isoproterenol-induced cardiac hypertrophy in iNOS knockout (KO) mice. Isoproterenol was continuously infused subcutaneously (15 mg/kg/day) using an osmotic minipump. Isoproterenol reduced body weight and fat mass in both iNOS KO and wild-type mice compared with saline-infused wild-type mice. Isoproterenol increased the heart weight in both iNOS KO and wild-type mice but there was no difference between iNOS KO and wild-type mice. Posterior wall thickness of left ventricle showed the same tendency with heart weight. Protein level of iNOS in the left ventricle was increased in isoproterenol-infused wild-type mice. The gene expression of interleukin-6 (IL-6) and transforming growth factor-beta (TGF-beta) in isoproterenol-infused wild-type was measured at 2, 4, 24, and 48-hour and isoproterenol increased both IL-6 (2, 4, 24, and 48-hour) and TGF-beta (4 and 24-hour). Isoproterenol infusion for 7 days increased the mRNA level of IL-6 and TGF-beta in iNOS KO mice, whereas the gene expression in wild-type mice was not increased. Phosphorylated form of extracellular signal-regulated kinases (pERK) was also increased by isoproterenol at 2 and 4-hour but was not increased at 7 days after infusion in wild-type mice. However, the increased pERK level in iNOS KO mice was maintained even at 7 days after isoproterenol infusion. These results suggest that deficiency of iNOS does not prevent isoproterenol-induced cardiac hypertrophy and may have potentially harmful effects on cardiac hypertrophy.
