To characterize the systemic and regional vascular effects of
atrial natriuretic peptide (
ANP) in chronic
heart failure, central hemodynamics, regional blood flow and plasma
ANP levels were determined in a rat model of
myocardial infarction and failure and in
sham-operated animals. Measurements were made in the conscious state before and after intravenous rANP [99-126] (8 micrograms bolus followed by continuous infusion of 1.0 microgram/kg/min). With this protocol,
ANP significantly decreased cardiac output, right atrial, left ventricular end-diastolic and arterial pressures and there were increases in heart rate, systemic and intestinal vascular resistances in
sham animals. Renal blood flow per gram of tissue was unchanged with
ANP, but when expressed as a percentage of cardiac output, increased significantly, indicating a preferential renal vasodilatory effect of
ANP. In rats with
infarction and failure, this dose did not alter cardiac output or arterial pressure, but decreased right atrial and left ventricular blood flow. Although significantly reduced as compared to the control group, renal blood flow was not improved with
ANP in the
heart failure group.
ANP plasma levels of the
heart failure group were elevated at baseline (p less than 0.01), and increased 5-10 times after infusion of rANP. Thus, in rats with chronic
heart failure, the renal vascular effects of
ANP are blunted, which may, in part, explain the failure of
ANP to restore the altered volume homeostasis in
heart failure despite elevated
ANP plasma levels. However, the effects on venous return were preserved which, in turn, improved cardiac performance via a reduction of preload.