Cardiac
natriuretic peptides consist of a family of six
peptide hormones that are synthesised by three separate genes and then stored as three separate prohormones (i.e. 126
amino acid atrial natriuretic peptide (
ANP), 108
amino acid B-type natriuretic peptide (BNP) and 103
amino acid C-type natriuretic peptide (CNP) prohormones). The
ANP prohormone contains four
peptide hormones:
long-acting natriuretic peptide (LANP),
vessel dilator,
kaliuretic peptide and
ANP. 2. Currently, the only
natriuretic peptide available commercially to treat
congestive heart failure (CHF) is BNP (
Nesiritide/
Natrecor; SCIOS, Sunnyvale, CA, USA), which causes a small increase in the urine volume of 90 38 mL/h compared with 67 27 mL/h and no significant natriuresis, but has beneficial haemodynamic effects in acute CHF individuals. These haemodynamic effects probably contribute to the side-effects of BNP in patients with acute CHF with a 27% incidence of
hypotension and possibly to 22% worsening of renal function, defined as an increase in serum
creatinine of 0.5 mg/dL, associated with a worse prognosis. A review of clinical trials suggests a twofold increased risk of death at 30 days post-
nesiritide treatment, a finding that needs further investigation. 3. The best of the
natriuretic peptides for treating chronic CHF is the
vessel dilator, which increases urinary flow up to 13-fold and
sodium excretion up to fourfold, without the previously mentioned side-effects. The natriuretic and
diuretic effects of vessel dilators last 6 h, which would allow them to be used on a four times per day basis in treating chronic CHF. 4.
Atrial natriuretic peptide does not cause significant improvement in
acute renal failure (ARF) in humans. The only
natriuretic peptide that significantly improves ARF is the
vessel dilator. Even when ARF has been established for 2 days before treatment in an ischaemic ARF animal model,
vessel dilator decreases serum
creatinine from 8.2 0.5 to 0.98 0.12 mg/dL in 6 days. At day 6 of ARF, mortality decreases to 14% (from 88%) without the
vessel dilator. After 6 days of treatment with the
vessel dilator, the proximal and distal tubules regenerate. 5. In
cancer,
vessel dilator, LANP,
kaliuretic peptide and
ANP at 1 mmol/L, decrease up to 97% of human breast, pancreatic and prostate
adenocarcinoma cells, as well as small cell and squamous cell
lung cancer cells within 24 h. In vivo,
vessel dilator, LANP and
kaliuretic peptide completely stop the growth of human pancreatic
adenocarcinomas in athymic mice and decrease their tumour volume by 49, 28 and 11%, respectively in 1 week.