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 natriuret ic peptides exist which include atrial natriuretic peptide (ANP) and b rain natriuretic peptide (BNP) of myocardial cell origin and C-type na triuretic peptide (CNP) of endothelial and renal epithelial cell origi n. 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 dete rmined in response to acute intravascular volume overload (AVO). Addit ionally, their functional role in cardiorenal regulation during AVO wa s investigated by utilizing the natriuretic peptide receptor antagonis t 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 gro ups demonstrated similar significant increases in right atrial pressur e, pulmonary capillary wedge pressure, pulmonary artery pressure and c ardiac output. Circulating ANP paralleled increases in right atrial pr essure and pulmonary capillary wedge pressure, with no changes in plas ma BNP or CNP. At peak AVO, urinary CNP excretion was increased compar ed with baseline (7.0+/-4.2 versus 62+/-8.0 pg/min, P < 0.05). 3. In t he 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 signi ficant attenuation of natriuresis (566 +/- 91 versus 24 +/- 198 mu Eq/ 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.