atrial natriuretic peptide (ANP) system. Cardiac ANP is secreted by atrial cells following volume expansion or in circumstances of elevated blood pressure. Table 15-7 summarizes the physiological actions of ANP.

2. Chemistry, Biosynthesis, and Secretion of ANP

There are three structural forms of the natriuretic peptides (NP), designated as atrial NP (ANP), brain NP (BNP), and C-type NP (CNP); the structural relationships are illustrated in Figure 15-10. Outside of the heart and brain (hypothalamus), some evidence of ANP gene expression has also been found in the lung, aortic arch, kidney, pituitary, and adrenal medulla. BNP was originally isolated from the brain, but now it is known that cardiac atrial cells secrete both ANP and BNP. CNP is believed to be produced only in the brain.

All three natriuretic peptides are characterized by a 17-member amino acid ring formed by a disulfide bridge between two cysteine residues. Each of the three natriuretic peptides is the product of a separate gene transcript.

The genes that code for ANP produce a prepro-ANP of 151 amino acids. Loss of the 25-amino-acid hydrophobic leader sequence generates a 126-amino-acid pro-ANP, which is stored in granules of the atrial myocytes. ANP is generated at the time of secretion by cleavage of the pro-ANP at Arg98-Ser99 to yield the mature peptide of 28 amino acid residues (residues 98-126 of prepro-ANP) and the N-terminal peptide (residues 1-98 of prepro-ANP). The N-terminal fragment is also secreted into the blood, but does not have any known biological activity. As yet the specific peptidases that process pro-ANP into ANP have not been characterized. The amino acid sequence of secreted ANP has been determined in many species and is identical in all except for position 110, where isoleucine replaces methionine in rat, mouse, and rabbit.

The secretion of ANF is stimulated by any of the following: (a) atrial stretch caused by volume expansion; (b) elevated blood pressure; (c) atrial tachycardia; and (d) high-salt diet.

3. Biological Actions of ANP

The several biological effects of ANP (see Table 157) include inhibition of angiotensin II stimulation of aldosterone biosynthesis, stimulation of the renal glomerulosa filtration rate (GFR) so as to promote Na+ natriuresis, and vasorelaxation; these are summarized in Figure 15-13. All of these biological effects are mediated by ANP binding to a specific outer cell membrane receptor. As shown in Figure 15-10 B, three distinct

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