Transgenic mice that carry fusions between the transcriptional regulatory sequences of atrial natriuretic factor (a hormone intimately involved in the regulation of blood pressure) and those encoding SV40 T antigen (an oncoprotein) were generated. Although both atria express the fusion gene, the pathological response to T antigen is asymmetrical. The right atrium undergoes a several hundredfold increase in mass while the left atrium remains relatively normal in size. Hyperplasia is accompanied by a progressive increase in both the frequency and severity of abnormalities in the atrial conduction system, which ultimately result in death.

http://science.sciencemag.org/content/sci/239/4843/1029.full.pdf

Atrial natriuretic factor-SV40 T antigen transgenes produce tumors and cardiac arrhythmias in mice

Maturing human pluripotent stem cell-derived cardiomyocytes in human engineered cardiac tissues

A schematic overview is presented as a framework for the more com­ prehensive review of the atrial peptide system that follows (Figure 1). An expanded discussion of the specific details and references is detailed in the subsequent section. Briefly, granules located in the atria (but not the ventri­ cles) contain the 126-amino acid prohormone termed atrial natriuretic factor (ANF) , atrial natriuretic peptide (ANP) , cardionatrin or atriopeptin (AP). cDNA probes have been used to characterize the amino acid sequence of a 152-amino acid rat atrial preprohormone. Non-atrial sites of AP synthesis have also been discovered in the central nervous system and the cardiac ventricle, which only expresses AP biosynthesis during fetal and neonatal development and during cardiac hypertrophy. Recently, Flynn and colleagues announced (at the Third International Congress on Biologically Active Atrial Peptides, New York, June 25-26, 1988) the isolation and sequencing from rat atrial extracts of a unique atriopeptin-like peptide termed iso-rANP (rat atrial natriuretic peptide) (Fig-

The biochemical pharmacology of atrial peptides

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are cardiac hormones, secreted by the atria and ventricles, respectively, in the normal adult heart. They participate in the regulation of blood pressure and body fluid homeostasis and modify growth and development of cardiovascular tissues and bone. Levels of ANP are higher in the fetal circulation than in adults, and fetal ventricles express higher levels of ANP and BNP than adult ventricles. The reappearance of ventricular ANP expression in adults is recognized as a marker of the induction of the embryonic gene program in ventricular hypertrophy. The natriuretic peptide system appears to be functional by midgestation, to respond to volume stimuli, and to regulate blood pressure and salt and water balance in the developing embryo. In addition, the natriuretic peptides may help regulate the blood supply to the fetus, acting as vasodilators in the placental vasculature. Peaks of ANP and BNP expression during gestation coincide with signi...

/pdf/minireview-natriuretic-peptides-during-development-of-the-kgpqcr098j.pdf

Minireview: Natriuretic Peptides during Development of the Fetal Heart and Circulation

To examine whether atrial natriuretic polypeptide (ANP) is released from the left ventricle in patients with dilated cardiomyopathy (DCM) we measured plasma ANP level in the aortic root (Ao), the anterior interventricular vein (AIV), the great cardiac vein (GCV), and the coronary sinus (CS) in 11 patients with DCM and 18 control subjects. Plasma ANP levels in Ao, AIV, GCV, and CS were 454 +/- 360, 915 +/- 584, 1,308 +/- 926, and 1,884 +/- 1,194 pg/ml, respectively, in the patients with DCM and 108 +/- 42, 127 +/- 55, 461 +/- 224, and 682 +/- 341 pg/ml, respectively, in the control subjects. There was no significant difference in the plasma ANP levels between Ao and AIV in the control subjects. On the contrary, there was a significant (P less than 0.001) step-up in plasma ANP levels between Ao and AIV in patients with DCM. Thus, the difference in ANP levels between Ao and AIV was significantly increased in patients with DCM as compared with the control subjects (461 +/- 248 vs. 19 +/- 59 pg/ml, P less than 0.001). The difference in ANP levels between Ao and CS was also significantly increased in patients with DCM as compared with the control subjects (1,429 +/- 890 vs. 577 +/- 318 pg/ml, P less than 0.001). We conclude that ANP is released in increased amounts into the circulation from the left ventricle as well as from the heart as a whole in patients with DCM.

/pdf/increased-secretion-of-atrial-natriuretic-polypeptide-from-2k24od9q9y.pdf

Increased secretion of atrial natriuretic polypeptide from the left ventricle in patients with dilated cardiomyopathy

We undertook a study of fetal synthesis, storage, and release of atriopeptin (AP). Plasma levels of both atriopeptin immunoreactivity (APir) and the NH2-terminal fragment of the prohormone immunoreactivity (NTFir) were very high in the fetus (4 and 20 times the maternal plasma, respectively). However, the atrial content of the AP was low, but surprisingly, ventricular content of AP was quite high (relative to the adult) in the fetus and fell postnatally. Atrial AP messenger RNA (mRNA) increased with postnatal age, whereas ventricular mRNA was extremely high in the fetus and fell rapidly after birth. High fetal plasma peptide levels may derive from the mother since infusion of exogenous atriopeptin 24 into the mother resulted in parallel increases in fetal and maternal peptide levels. Fetal plasma APir and NTFir levels partially reflect the markedly reduced total renal metabolic capacity compared with that of the adult. Plasma levels fell progressively after birth; whereas neonatal atrial content rose substantially. Plasma AP and NTF were simultaneously elevated in both the maternal and fetal circulation after vasopressin injection of the mother. The fetus can also respond to exogenous stimuli (vasopressin or indomethacin--presumably via ductal closure) and promptly release substantial amounts of peptide into its circulation. Thus, it appears that the AP hormonal system is functional during fetal life and responds avidly to increases in intracardiac pressure as does the mature animal.

/pdf/developmental-changes-in-the-rat-atriopeptin-hormonal-system-2cxxqymeva.pdf

Y F Wei

Papers

Developmental changes in the rat atriopeptin hormonal system.