Differential regulation of natriuretic peptide receptor messenger RNAs during the development of cardiac hypertrophy in the rat

• Published in: The Journal of clinical investigation Vol. 92; no. 6; pp. 2702 - 2712
• Main Authors: BROWN, L. A, NUNEZ, D. J. R, WILKINS, M. R
• Format: Journal Article
• Language: English
• Published: Ann Arbor, MI American Society for Clinical Investigation 01-12-1993
• Subjects: Animals; Base Sequence; Biological and medical sciences; Cardiology. Vascular system; Cardiomegaly - metabolism; Cardiomegaly - physiopathology; Cardiopathies: etiologic forms (general aspects and miscellaneous); DNA Primers; DNA, Complementary - metabolism; Gene Expression Regulation; Guanylate Cyclase - metabolism; Heart; Male; Medical sciences; Molecular Sequence Data; Myocardium - metabolism; Oligonucleotides, Antisense; Polymerase Chain Reaction - methods; Polymorphism, Genetic; Rats; Rats, Wistar; Receptors, Atrial Natriuretic Factor - biosynthesis; Reference Values; RNA, Messenger - biosynthesis; RNA, Messenger - metabolism; Time Factors; Brain natriuretic peptide; Cardiac performance; Arteriovenous shunt; Pathophysiology; Rat; Peptide hormone; Rodentia; Cardiovascular disease; Atrial natriuretic peptide; Gene expression; Vertebrata; Experimental disease; Natriuretic hormone; Mammalia; Animal; Myocardium; Hypertrophy; Hormonal receptor
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI116887

The heart expresses the three natriuretic peptide receptors (NPR), namely NPR-A, NPR-B, and NPR-C. We have examined the temporal relationship between the expression of mRNA transcripts for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and their receptors in the heart during the development of cardiac hypertrophy in the aortovenocaval fistula rat. Messenger RNAs were measured by cDNA amplification. Progressive cardiac hypertrophy was accompanied by increased ANP mRNA prevalence throughout the heart and increased BNP mRNA in the left atrium. The most striking observation was the gradual disappearance of NPR-C transcripts (the putative "clearance" receptor) in all chambers; this was in marked contrast to the increase in mRNA levels for NPR-A and NPR-B (the guanylyl cyclase-linked receptors). Our observations have important therapeutic implications if the transcript changes are mirrored at the receptor protein level because (a) the apparent down-regulation of NPR-C may enhance the local action of natriuretic peptides on the heart, and (b) the loss of NPR-C, particularly if it is widespread, may reduce the rate of elimination of the natriuretic peptides, restricting the therapeutic potential of specific NPR-C ligands designed to reduce peptide clearance.