Chronic vs acute hemodynamic effects of atrial natriuretic factor in conscious rats
Description
The present study was designed to examine the chronic (5 day) and acute (2 hr) hemodynamic effects of atrial natriuretic factor (ANF) in conscious normotensive rats. Exogenous ANF was infused to mimic the plasma levels which are found under pathologic conditions such as heart failure. Control (CON) measurements were taken following one day of vehicle infusion. Rats were then infused with either vehicle (n = 11) or ANF (100 ng/kg/min; n = 9) i.v. for 5 days. Mean arterial pressure (MAP) in the ANF infused group fell significantly from a CON value of 114 $\pm$ 2 to 100 $\pm$ 3 and 99 $\pm$ 2 mmhg on days 1 and 5, respectively. Total peripheral resistance (TPR) increased (21 $\pm$ 5%) and cardiac output (CO) significantly decreased (27 $\pm$ 2%) on day 1 of the ANF infusion; neither variable was significantly different from CON on day 5. Plasma immunoreactive ANF (IR-ANF) levels were significantly elevated from 94 $\pm$ 10 (CON) to 626 $\pm$ 202 pg/ml (Day 5) Acute infusion (2 hr) of ANF (100 ng/kg/min; n = 15) resulted in an attenuated hypotensive effect when compared to chronic ANF infusion. MAP decreased only 5 $\pm$ 3 mmhg, which was associated with a 23 $\pm$ 4% decrease in CO and 27 $\pm$ 6% increase in TPR at 120 min. Hematocrit increased from 41.9 $\pm$ 0.7% to 46.0 $\pm$ 0.6% at 120 min of ANF infusion. Plasma IR-ANF levels were significantly elevated from 148 $\pm$ 17 (VEH) to 791 $\pm$ 76 pg/ml (ANF, 2 hrs). There were no significant effects of chronic or acute vehicle infusion In summary, chronic infusion of ANF which elevated IR-ANF plasma levels into the pathophysiologic range produced a significant hypotensive effect in normotensive rats. A significant fall in CO mediated the fall in blood pressure on day 1 of the infusion. The hemodynamic alterations which produced the sustained drop in MAP seen on day 5, were independent of changes in intravascular volume, but may have been due to autoregulatory phenomena which returned CO to control levels and caused a reduction in TPR. Acute infusion of ANF produced a modest decrease in MAP which was due to a contraction of the vascular volume and a decrease in CO. Greater elevations in TPR during the acute infusion of ANF may have partially offset the early drop in MAP. These findings suggest that chronic elevations of plasma ANF may decrease afterload in conditions such as heart failure without compromising CO