Therapeutic actions of a new synthetic vasoactive and natriuretic peptide,dendroaspis natriuretic peptide, in experimental severe congestive heart failure

Dendroaspis natriuretic peptide (DNP), a recently discovered peptide, share s structural similarity to the other known natriuretic peptides, ANP, BNP, and CNP. Studies have reported that DNP is present in human and canine plas ma and atrial myocardium and increased in plasma of humans with congestive heart failure (CHF). In addition, synthetic DNP is markedly natriuretic and diuretic and is a potent activator of cGMP in normal animals. To date, the ability of synthetic DNP to improve cardiorenal function in experimental C HF is unknown. Synthetic DNP was administered intravenously at 10 and 50 ng . kg-(1) . min(-1) in dogs (n=7) with severe CHF induced by rapid ventricu lar pacing for 10 days at 245 bpm. In addition, we determined endogenous DN P in normal (n=4) and failing (n=4) canine atrial and ventricular myocardiu m. We report that administration of synthetic DNP in experimental severe CH F has beneficial cardiovascular, renal, and humoral properties. First, DNP in CHF decreased cardiac filling pressures, specifically right atrial press ure and pulmonary capillary wedge pressure. Second, DNP increased glomerula r filtration rate in association with natriuresis and diuresis despite a re duction in mean arterial pressure. Third. DNP increased plasma and urinary cGMP and suppressed plasma renin activity. Fourth and finally, we report th at DNP immunoreactivity is present in canine atrial and ventricular myocard ium and increased in CHF. These studies report the acute intravenous action s of synthetic DNP in experimental severe CHF and suggest that on the basis of its beneficial properties, DNP may have potential as a new intravenous agent for the treatment of decompensated CHF.