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, shares structural similarity to the other known natriuretic peptides, ANP, BNP, and CNP. Studies have reported that DNP is present in human and canine plasma 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 CHF 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 ventricular pacing for 10 days at 245 bpm. In addition, we determined endogenous DNP in normal (n=4) and failing (n=4) canine atrial and ventricular myocardium. We report that administration of synthetic DNP in experimental severe CHF has beneficial cardiovascular, renal, and humoral properties. First, DNP in CHF decreased cardiac filling pressures, specifically right atrial pressure and pulmonary capillary wedge pressure. Second, DNP increased glomerular filtration rate in association with natriuresis and diuresis despite a reduction in mean arterial pressure. Third, DNP increased plasma and urinary cGMP and suppressed plasma renin activity. Fourth and finally, we report that DNP immunoreactivity is present in canine atrial and ventricular myocardium and increased in CHF. These studies report the acute intravenous actions 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.
Lisy
O
O
Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Departments of Physiology and Internal Medicine, Mayo Clinic and Foundation, Rochester, MN 55905, USA. lisy.ondrej@mayo.edu
Lainchbury
J G
JG
Leskinen
H
H
Burnett
J C
JC
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002317:Cardiovascular Agents / Q000378:metabolism / Q000627:therapeutic use*; D006152:Cyclic GMP / Q000097:blood; D004285:Dogs; D004546:Elapid Venoms / Q000378:metabolism / Q000627:therapeutic use*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006439:Hemodynamics; D036341:Intercellular Signaling Peptides and Proteins; D007684:Kidney Tubules / Q000502:physiology; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010455:Peptides / Q000378:metabolism / Q000627:therapeutic use*; D011669:Pulmonary Wedge Pressure / Q000502:physiology; D011863:Radioimmunoassay; D012083:Renin / Q000097:blood
D002317:Cardiovascular Agents; C075597:Dendroaspis natriuretic peptide; D004546:Elapid Venoms; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D012083:Renin; D006152:Cyclic GMP