Ontogeny of atrial natriuretic polypeptide in the human heart

Abstract

To elucidate the developmental changes of atrial natriuretic polypeptide in the human heart, we studied \g=a\-humanatrial natriuretic polypeptide (\g=a\-hANP)-likeimmunoreactivity (\g=a-hANP-LI) in the extracts from the hearts of three foetuses of 10, 14 and 22 weeks' gestation, a 1-day-old premature infant of 33 weeks' gestation, and two adults. \g=a\-hANP-LIlevels in the atria of the three foetuses of 10, 14 and 22 weeks' gestation and the premature infant (31.4, 12.2, 9.25 and 15.3 nmol/g, respectively) were comparable to those in two adult atria (16.9 and 13.6 nmol/g). The ventricles also contained \g=a\-hANP-LI (0.763 \ar=r\0.0818 nmol/g with descending values with increasing gestational age) in the three foetuses and the premature infant although it was undetectable (< 0.0162 nmol/g) in two adult ventricles. The highest \g=a\-hANP-LIconcentration was observed in the auricles in all the hearts except in the premature infant. The concentration in the right auricle was higher than in the left during foetal life, whereas that in the left was the higher one after birth. High performance gel permeation chromatography coupled with radioimmunoassay revealed that \g=a\-hANP\x=req-\ LI in the atria and apexes of the foetuses and the premature infant consisted of \g=a\hANP,\g=b\-hANP and \g=a\-hANP,with \g=g\-hANPbeing the predominant form. Essentially similar gel filtration patterns were observed in the two adult atria. These results indicate that: 1) ANP appears in human heart tissue early in foetal life;2) cardiac ventricles also contain ANP in the foetus, and 3) there is probably no difference in posttranslational processing of the precursor molecule in foetal and adult hearts.

Synthesis of atrial natriuretic polypeptide in human failing hearts. Evidence for altered processing of atrial natriuretic polypeptide precursor and augmented synthesis of beta-human ANP.

“…Kangawa and Matsuo also showed that synthetic ahANP, despite its exposure to the conditions used for the extraction, did not undergo dimerization to f3-hANP (4 We and others previously reported that the predominant component of ANP in the rat heart is y-rat ANP (14, 15), whereas fl-hANP and a-hANP are present together with yhANP in human atrial tissues obtained at cardiac surgery or autopsy (4,14,15). However, our subsequent study revealed that the predominant molecular form ofANP in atria obtained at autopsy from patients without heart diseases, from foetuses and from premature infants is -y-hANP (41). These results suggest that the major storage form of ANP in the human normal heart is y-hANP like in rats.…”

Augmented expression of atrial natriuretic polypeptide gene in ventricle of human failing heart.

“…A The gene expression of ANP in the ventricle has been reported to be increased in neonatal rats and decreased during the first week of life (18). We have also reported that the ANP concentration in the ventricle is more than 1 4tg/g in human fetuses at 14 and 22 wk gestation, that it decreases in parallel with fetal development, and that adult ventricle contains < 50 ng/g of ANP (35). These results indicate that the expression of the ANP gene is reinduced in the ventricle of patients with CHF.…”

Growth and partial differentiation of presumptive human cardiac myoblasts in culture.

“…Atrial natriuretic factor is expressed at very high levels in fetal atrium and ventricle (Block et al, 1986;Kikuchi et al, 1987), and is restricted to myocardial cells in the heart (Hamid et al, 1987). Induction of ANF expression was identified in this study as a marker for the differentiation of cardiac myoblasts in culture.…”