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Cardiovascular Research 1997 36(3):363-371; doi:10.1016/S0008-6363(97)00192-2
© 1997 by European Society of Cardiology
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Copyright © 1997, European Society of Cardiology

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

Lesley A Browna, Richard A.D Rutherfordb, Derek J.R Nuneza, John Whartonb, David G Lowec and Martin R Wilkinsa,*

aDepartment of Clinical Pharmacology, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Rd, London W12 0NN, UK
bDepartment of Histochemistry, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Rd, London W12 0NN, UK
cGenentech Inc., South San Francisco, CA, USA

* Corresponding author: Tel.: +44 181 7403219; Fax: +44 181 7493439; E-mail: mwilkins@rpms.ac.uk

Objectives: 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. Methods: 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. Results: Western blot analysis revealed a single band (~120 kDa) in ventricular membranes which was reduced to ~60 kDa after treatment with β-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. Conclusions: 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.

KEYWORDS Rat; Volume overload; Cardiac hypertrophy; Autoradiography; Immunocytochemistry


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