[Molecular mechanism of nitric oxide in preventing cardiomyocytes from hypertrophic response induced by angiotensin II].
The aim of this study was to determine the molecular mechanism of nitric oxide (NO) in preventing cardiomyocytes from hypertrophic response induced by angiotensin II (Ang II). Hypertrophic response of neonatal rat cardiomyocytes was assayed by protein synthesis rate and expression of atrial natriuretic peptide (ANP) mRNA. The level of NO was shown by the content of nitrate and nitrite in cardiac myocytes. The protein expression of MKP-1 and the gene expression of eNOS were measured with Western blotting and RT-PCR, respectively. The results are as follows. (1) L-arginine (L-Arg) induced a dose-dependent increase in NO by 16% and 31% at the concentrations of 10 micromol/L and 100 micromol/L, respectively. L-Arg also increased the gene expression of eNOS. However, these effects were inhibited by L-NAME, the inhibitor of NOS. (2) The gene expression and the protein synthesis of ANP induced by Ang II (0.1 micromol/L) were inhibited by L-Arg (100 micromol/L). The inhibitory action of L-Arg was abolished after pretreatment with antisense oligoneucleotide against MKP-1. (3) L-Arg (100 micromol/L) increased the protein expression of MKP-1 by 225%, which was inhibited by L-NAME, an NOS inhibitor, and KT-5823, a cGMP-dependent protein kinase (PKG) inhibitor. However, Ang II enhanced the effect induced by L-Arg. The above results show that NO may activate PKG, and thereby promote the protein expression of MKP-1 and inactivate MAPK, resulting in an inhibition of cardiomyocyte hypertrophic response induced by Ang II.
Liu
Pei-Qing
PQ
Department of Physiology, Sun Yat-Sen University of Medical Sciences, Guangzhou 510089, China. Jing@gzsums.edu.cn
Lu
Wei
W
Pan
Jing-Yun
JY
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001120:Arginine / Q000494:pharmacology; D006332:Cardiomegaly / Q000378:metabolism* / Q000503:physiopathology; D005656:Fungal Proteins; D066298:In Vitro Techniques; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
D005656:Fungal Proteins; D000804:Angiotensin II; D009569:Nitric Oxide; D001120:Arginine; D020928:Mitogen-Activated Protein Kinases