Transcription of Brain Natriuretic Peptide and Atrial-natriuretic-peptide Genes in Human Tissues

We have compared the expression of atria1 natriuretic peptide (ANP) and brain natriuretic peptide (BNP) genes in various human tissues using a quantitative polymerase chain reaction technique. Tissues of three human subjects, obtained at autopsy, were analyzed. BNP transcripts could be detected in the central nervous system, lung, thyroid, adrenal, kidney, spleen, small intestine, ovary, uterus, and striated muscle. ANP transcripts could also be demonstrated in various human extracardiac tissues including several endocrine organs. In all periphera1 tissues, the level of both natriuretic peptide transcripts was approximately l-2 orders of magnitude lower than in cardiac ventricular tissues. This distribution is in marked contrast to the much lower level of ANP and BNP transcripts present in extracardiac rat tissues (generally less than l/1000 of ventricles). These data suggest differential expression of the two natriuretic peptide genes in cardiac and extracardiac tissues in man. Furthermore, the presence of local synthesis of ANP and BNP in various peripheral organs su gests paracrine and/or autocrine function of these natriuretic pepti es. (J Clin Endocrinol 2 Metab 78:1307-1311,1994) T HE CARDIAC hormones atria1 natriuretic peptide (ANP) and brain natriuretic peptide (BNP) exhibit similar pharmacological profiles, such as natriuresis and smooth muscle relaxation (1). Along with these common properties there are striking dissimilarities: Whereas the structure of ANP is highly conserved among different species, there is considerable variation of the amino acid sequence of BNP. Furthermore, there are differences regarding their tissue distribution. The heart is the major site of synthesis of ANP, but low levels of ANP transcription have also been found in various other tissues of different species (2-13), including human where ANP messenger RNA (mRNA) has been detected in heart (2) and thymus (12). Although originally identified and isolated from the porcine brain (14) BNP has been shown to be mainly a cardiac hormone; in fact, all BNP complimentary DNA (cDNAs), porcine (15, 16), rat (17), and human (18) were isolated from cardiac cDNA libraries. Tissue distribution of BNP has been studied in rat at the peptide (19-21) and mRNA (22) levels. In human, BNP peptide was described in atria and ventricles (23-25) and more recently in brain (26). Received July 20, 1993. Accepted February 1, 1994. Address correspondence and requests for reprints to: Priv. Doz. Dr. Alexander L. Gerbes, Medizinische Klinik II, Klinikum Grosshadern, Universitit Miinchen, MarchioninistraBe 15, 81366 Munchen, Federal Republic of Germany. * Parts of these data were presented at the Ninth International Congress of Endocrinology, Nice, France, September 1992. This work was supported by the Medical Research Council and the Heart and Stroke Foundation of Canada (to M.N.). t Supported by a ASCHE stipendium of the Deutsche Gesellschaft fiir Verdauungsund Stoffwechselkrankheiten and by the Fond de la Recherche en Sante de Quebec. $ Fellow of the HSFC. 5 Recipient of a summer bursary from the FRSQ. 1 McDonald scholar of the HSFC. The presence of BNP immunoreactivity in human (26) and porcine (14) but not rat (19, 21) brain raises the question of species specific distribution of the peptide. Therefore we undertook the analysis of ANP and BNP gene expression in extracardiac human tissues using quantitative PCR amplification of human ANP and BNP transcripts, Subjects and Methods