Actions of a novel synthetic natriuretic peptide on hemodynamics and ventricular function in the dog.
Dendroaspis natriuretic peptide (DNP) is a recently discovered peptide with structural similarity to known natriuretic peptides. DNP has been shown to possess potent renal actions. Our objectives were to define the acute hemodynamic actions of DNP in normal anesthetized dogs and the acute effects of DNP on left ventricular (LV) function in conscious chronically instrumented dogs. In anesthetized dogs, DNP, but not placebo, decreased mean arterial pressure (141 +/- 6 to 109 +/- 7 mmHg, P < 0.05) and pulmonary capillary wedge pressure (5.8 +/- 0.3 to 3.4 +/- 0.2 mmHg, P < 0.05). Cardiac output decreased and systemic vascular resistance increased with DNP and placebo. DNP-like immunoreactivity and guanosine 3',5'-cyclic monophosphate concentration increased without changes in other natriuretic peptides. In conscious dogs, DNP decreased LV end-systolic pressure (120 +/- 7 to 102 +/- 6 mmHg, P < 0.05) and volume (32 +/- 6 to 28 +/- 6 ml, P < 0.05) and LV end-diastolic volume (38 +/- 5 to 31 +/- 4 ml, P < 0.05) but not arterial elastance. LV end-systolic elastance increased (6.1 +/- 0.7 to 7.4 +/- 0.6 mmHg/ml, P < 0.05), and Tau decreased (31 +/- 2 to 27 +/- 1 ms, P < 0.05). The effects on hemodynamics, LV function, and second messenger generation suggest synthetic DNP may have a role as a cardiac unloading and lusitropic peptide.
Lainchbury
John G
JG
Cardiorenal Research Laboratory, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Lisy
Ondrej
O
Burnett
John C
JC
Meyer
Donna M
DM
Redfield
Margaret M
MM
D000758:Anesthesia; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D002302:Cardiac Output / Q000187:drug effects; D003243:Consciousness; D006152:Cyclic GMP / Q000097:blood; D003971:Diastole / Q000187:drug effects; D004285:Dogs; D004546:Elapid Venoms / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D013599:Systole / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects*
C075597:Dendroaspis natriuretic peptide; D004546:Elapid Venoms; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP