Activation of myocardial and renal natriuretic peptides during acute intravascular volume overload in dogs: functional cardiorenal responses to receptor antagonism.

1. A family of structurally related but genetically distinct natriuretic peptides exist which include atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) of myocardial cell origin and C-type natriuretic peptide (CNP) of endothelial and renal epithelial cell origin. All three exert actions via cGMP, with ANP and BNP functioning via the natriuretic peptide A receptor and CNP via the natriuretic peptide B receptor. 2. Circulating and urinary natriuretic peptides were determined in response to acute intravascular volume overload (AVO). Additionally, their functional role in cardiorenal regulation during AVO was investigated by utilizing the natriuretic peptide receptor antagonist HS-142-1. Control (n=5) and study dogs (HS-142-1, n=9) underwent AVO with normal saline equal to 10% of body weight over 1 h. Both groups demonstrated similar significant increases in right atrial pressure, pulmonary capillary wedge pressure, pulmonary artery pressure and cardiac output. Circulating ANP paralleled increases in right atrial pressure and pulmonary capillary wedge pressure, with no changes in plasma BNP or CNP. At peak AVO, urinary CNP excretion was increased compared with baseline (7.0+/-4.2 versus 62+/-8.0 pg/min, P<0.05). 3. In the HS-142-1-treated group, plasma cGMP was decreased compared with the control group (9.6+/-1.1 to 5.0+/-1.2 pmol/ml, P<0.05). A significant attenuation of natriuresis (566+/-91 versus 1241+/-198 microEq/min, P<0.05) and diuresis (4.8+/-0.7 versus 10.1+/-2.0 ml/min, P<0.05) was also observed at peak AVO in the HS-142-1 treated group. 4. These findings support differential and selective responses of the three natriuretic peptides to AVO, in which plasma ANP and urinary CNP are markers for AVO. Secondly, these studies confirm the role of ANP and CNP but not BNP in the natriuretic and diuretic response to acute volume overload.