Mammalian atrial extracts possess natriuretic and diuretic activity. In experiments reported here it was found that atrial, but not ventricular, extract also causes relaxation of isolated vascular and nonvascular smooth muscle preparations. The smooth muscle relaxant activity of atrial extract was heat-stable and concentration-dependent and could be destroyed with protease. Rabbit aortic and chick rectum strips were used for the detection of atrial biological activity. The atrial activity was separated by column chromatography into two peaks having apparent molecular weights of 20,000 to 30,000 and less than 10,000. The atrial substance that copurified with the smooth muscle relaxant activity in both peaks caused natriuresis when injected into conscious rats. It appears that atria possess at least two peptides that elicit smooth muscle relaxation and natriuresis, suggesting an endogenous system of fluid volume regulation.

Mammalian cardiac atria have several biologically active peptides that exert profound effects on sodium excretion, urine volume, and smooth muscle tone. In the present study two such peptides of low molecular weight were purified and separated from each other on the basis of differences in charge, hydrophobicity, and biological profile. The first peptide, designated atriopeptin I, exhibits natriuretic and diuretic activity and selectivity relaxes intestinal smooth muscle but not vascular smooth muscle strips. The second peptide, atriopeptin II, is a potent natriuretic and diuretic that relaxes both intestinal and vascular strips. Sequence analysis of atriopeptin I indicates that it is composed of 21 amino acids, of which serine and glycine residues predominate. The amino terminal sequence of atriopeptin II up to residue 21 is the same as that of atriopeptin I, with the addition of the Phe-Arg extension at the carboxyl terminus. Both peptides appear to be derived from a common high molecular weight precursor (designated atriopeptigen); their biological selectivity and potency may be determined by the site of carboxyl terminal cleavage.

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We undertook a study of fetal synthesis, storage, and release of atriopeptin (AP). Plasma levels of both atriopeptin immunoreactivity (APi,) and the NH2-terminal fragment of the prohormone immunoreactivity (NTFf,) 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. Introduction Atriopeptins (AP)' are spasmolytic, natriuretic, and diuretic peptides found in adult mammalian cardiac atria (1, 2). The peptides have multiple effects, including inhibition of aldosterone, renin and vasopressin release, reduction in systemic blood pressure and enhancement of renal glomerular filtration rate (reviewed in references 3-6). AP release can be stimulated by volume expansion (6) or agents, including 1-desamino-arg8-va-

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