Effects of long-term increases in plasma ANP on angiotensin II-induced hypertension

In vitro studies have suggested that atrial natriuretic peptide (ANP) is a potent antagonist of the vasoconstrictor actions of angiotensin II (ANG II). The purpose of this study was to determine the long-term effects of physiological increases in circulating levels of ANP on arterial pressure (AP) regulation in conscious dogs (n = 9) with ANG II-induced hypertension. Infusion of ANG II at a rate of 10 ng.kg-1.min-1 for 7 days increased AP from 85 +/- 3 to 133 +/- 4 mmHg. This increase in AP was associated with an increase in total peripheral resistance (TPR) and a decrease in cardiac output (CO). After 7 days of ANG II infusion, ANP103-126 was then infused simultaneously at a rate of 20 ng.kg-1.min-1 for 7 days. Plasma levels of ANP increased from 59 +/- 15 to 285 +/- 28 pg/ml. Increasing plasma ANP levels for 7 days had no significant long-term effect on AP (133 +/- 4 vs. 125 +/- 6 mmHg), TPR, or CO. There were also no significant changes in glomerular filtration rate or sodium excretion during the 7 days of ANP infusion. These data indicate that long-term increases in circulating levels of ANP have minimal chronic hypotensive effects in dogs with ANG II hypertension. In addition, the results from this study suggest that physiological increases in plasma ANP do not exhibit long-term antagonistic effects toward the vasoconstrictor actions of ANG II.