MECHANISM OF DECREASED CARDIAC-OUTPUT DURING ANP INFUSION IN CONSCIOUS ANEPHRIC DOGS

Atrial natriuretic peptide (ANP) may decrease cardiac output (CO) by lowering circulating blood volume (BV) or by altering the vasculature in a manner that would decrease venous return. The purpose of this study was to determine the role of decreased BV in mediating the decrease in CO during acute infusion of ANP. BV was measured by dilution of Cr-51-labeled red blood cells in seven trained conscious splenectomized dogs studied after unilateral (UNX) and total (TNX) nephrectomy. BV, hematocrit (Hct), CO, mean arterial pressure (MAP), and total peripheral resistance (TPR) were determined during a 90-min control period and 270 min of infusion of ANP (20 ng.kg-1.min-1 iv). In UNX dogs, ANP decreased BV from 60.9 +/- 1.4 to 58.6 +/- 1.4 ml/kg and increased Hct from 39.3 +/- 1.8% to 41.1 +/- 1.8% (P < 0.05). MAP was not changed and CO fell to a low that was 86 +/- 2% of control (P < 0.05) 240 min after starting ANP. TPR increased significantly during ANP infusion. All variables returned to control after ANP was stopped. In the same dogs studied 24 h after TNX, MAP averaged 111 +/- 5 mmHg during control and did not change during ANP infusion. CO fell to a low of 82 +/- 3% of control (P < 0.05) after 120 min of infusion and remained reduced until after the ANP was stopped. TPR increased from 37 +/- 4 mmHg.l-1.min during control to a peak of 45 +/- 5 mmHg.l-1.min at 120 min (P < 0.05). BV was 60.2 +/- 3.8 ml/kg during control and averaged 60.1 +/- 3.7, 59.4 +/- 3.6, and 59.9 +/- 3.8 ml/kg after 90, 180, and 270 min of ANP infusion, respectively; Hct was unchanged. These results suggest that in TNX dogs, acute infusion of ANP, at pathophysiological levels, decreases CO independent of changes in BV. The decrease in CO may be due to a reduction in venous return secondary to an increase in resistance to venous return.