Downregulation of natriuretic peptide C-receptor protein in the hypertrophied ventricle of the aortovenocaval fistula rat

• Published in: Cardiovascular research Vol. 36; no. 3; pp. 363 - 371
• Main Authors: BROWN, L. A, RUTHERFORD, R. A. D, NUNEZ, D. J. R, WHARTON, J, LOWE, D. G, WILKINS, M. R
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.12.1997
• Subjects: Animals; Arteriovenous Fistula - complications; Arteriovenous Fistula - metabolism; Autoradiography; Biological and medical sciences; Blotting, Western; Cardiology. Vascular system; Cardiomegaly - etiology; Cardiomegaly - metabolism; Down-Regulation; Guanylate Cyclase - metabolism; Heart; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Immunohistochemistry; Male; Medical sciences; Myocardium - metabolism; Protein Binding; Rats; Rats, Wistar; Receptors, Atrial Natriuretic Factor - metabolism; Rat; Immunocytochemistry; Pathogenesis; Rodentia; Cardiovascular disease; Heart ventricle; Pathology; Autoradiography; Vertebrata; Mammalia; Natriuretic hormone; Heart disease; Animal; Hypertrophy; Biological receptor
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1016/S0008-6363(97)00192-2

This study examined the expression of the C-type receptor for the natriuretic peptide family (NPR-C) in the ventricles of normal and aortovenocaval (AV)-fistula rats, the latter a model of cardiac volume overload producing hypertrophy of both ventricles. Western blotting with a rabbit anti-NPR-C antibody was used to quantify NPR-C levels in ventricular membranes. NPR-C expression was localised anatomically and measured in frozen sections of cardiac tissue by histochemistry and in vitro autoradiography. Western blot analysis revealed a single band (approximately 120 kDa) in ventricular membranes which was reduced to approximately 60 kDa after treatment with beta-mercaptoethanol. NPR-C immunoreactivity and [125I]rat ANP1-28 binding (displaceable by the NPR-C-specific ligand C-ANP 4-23) were localised to the endocardium. NPR-C protein levels, as measured by all three techniques, were reduced significantly in the hypertrophied ventricles of AV-fistula rats compared to sham-operated animals. Volume-induced cardiac hypertrophy in the AV-fistula rat is associated with downregulation of endocardial NPR-C. This may be one mechanism by which the endocardium regulates the myocardial response to changes in haemodynamic load.