Peptides

PEPTIDES

There is growing interest in the natriuretic peptides (ANP, BNP, and CNP,), which induce natriuresis through sev-eral different mechanisms. ANP and BNP are synthesized in the heart, while CNP comes primarily from the CNS. Some of these peptides exert both vascular effects  and sodium transport effects in the kidney, which participate in causing natri-uresis. A fourth natriuretic peptide, urodilatin, is structurally very similar to ANP but is synthesized and functions only in the kid-ney. Urodilatin is made in distal tubule epithelial cells and blunts Na⁺ reabsorption through effects on Na⁺ uptake channels and Na⁺/K⁺-ATPase at the downstream collecting tubule system. In addition, through effects on vascular smooth muscle, it reduces glomerular afferent and increases glomerular efferent vasomotor tone. These effects cause an increase in GFR, which adds to the natriuretic activity. Ularitide is a recombinant peptide that mimics the activity of urodilatin. It is currently under intense investiga-tion and may become available for clinical use in the near future.

The cardiac peptides ANP and BNP have pronounced systemic vascular effects. The receptors ANP_A and ANP_B, also known as NPR_A and NPR_B, are transmembrane molecules with guanylyl cyclase cata-lytic activity at the cytoplasmic domains. Of interest, both peptides increase GFR through effects on glomerular arteriolar vasomotor tone and also exhibit diuretic activity. CNP has very little diuretic activity. Three agents in this group are in clinical use or under investigation: nesiritide (BNP), carperitide (ANP, available only in Japan), and ular-itide (urodilatin, under investigation). Intravenous ularitide has been studied extensively for use in acute heart failure. It can dramatically improve cardiovascular parameters and promote diuresis without reducing creatinine clearance. There is also evidence that nesiritide (simulating BNP) may enhance the activity of other diuretics while helping to maintain stable renal function.