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Natriuretic Peptide Receptor‐C Agonist Attenuates the Enhanced Expression of Gqα, PLCβ1 Proteins and Vascular Smooth Muscle Cell Hypertrophy From Spontaneously Hypertensive Rats: Role of ROS and ROS‐Mediated Signalling
Author(s) -
Jain Ashish,
AnandSrivastava Madhu B
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.941.11
Subject(s) - vascular smooth muscle , medicine , p22phox , atrial natriuretic peptide , endocrinology , nadph oxidase , muscle hypertrophy , nox4 , agonist , gq alpha subunit , receptor , g protein , chemistry , natriuretic peptide , brain natriuretic peptide , biology , oxidative stress , heart failure , smooth muscle
Hypertension is associated with vascular remodelling due to hyper‐proliferation and hypertrophy of vascular smooth muscle cells (VSMCs). We earlier showed the implication of enhanced expression of Gqα and PLCβ1 proteins in VSMCs from 16‐week‐old spontaneously hypertensive rats (SHR). The present study was undertaken to investigate whether C‐ANP 4–23 , a natriuretic peptide receptor‐C (NPR‐C) agonist that has been shown to inhibit vasoactive peptide‐induced enhanced protein synthesis in VSMCs, could attenuate VSMC hypertrophy in rat models of cardiac hypertrophy and to explore the underlying mechanisms contributing to this inhibition. For these studies, aortic VSMCs from 16‐week‐old SHR were used. The protein synthesis, a marker of hypertrophy, was determined by ( 3 H) leucine incorporation and the expression of proteins was determined by Western blotting. The protein synthesis was significantly enhanced in VSMC from SHR as compared to WKY and C‐ANP 4–23 treatment attenuated the enhanced protein synthesis to WKY control levels. In addition, the enhanced expression of Gqα and PLCβ1 proteins in VSMC's from SHR was attenuated by C‐ANP 4–23 treatment. Furthermore, C‐ANP 4–23 also attenuated the enhanced levels of superoxide anion (O 2 − ), NADPH oxidase activity, the increased expression of NOX4, p47phox and p22phox, as well as the enhanced phosphorylation of ERK1/2, AKT1/2 and c‐Src. In conclusion, these results indicate that C‐ANP 4–23 , via the activation of NPR‐C, attenuates VSMC hypertrophy through its ability to decrease the over‐expression of Gqα, PLCβ1 proteins, enhanced oxidative stress and MAPK/AKT signalling pathway. Thus, it can be suggested that C‐ANP 4–23 , an activator of NPR‐C, may be used as a therapeutic agent for the treatment of vascular complications associated with hypertension and atherosclerosis Support or Funding Information Supported by grants from Canadian Institutes of Health Research and Heart and Stroke Foundation of Canada.