Cardiac and hemodynamic responses to synthetic atrial natriuretic factor in rats

Abstract

To determine the hemodynamic effects of a hypotensive dose of atrial natriuretic factor (ANF), a synthetic peptide containing 26 amino acids of endogeneous rat ANF (Arg-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Gly-Ala-Gln-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-C00H) was studied in two groups of barbiturate anesthetized rats. In the first experiment, a 20-minute infusion of a hypotensive dose, 95 pmole/min i.v., of the synthetic ANF decreased mean arterial pressure (MAP) by 40 + 3 mm Hg from a baseline of 128 + 5 mm Hg, and cardiac output (CO) (microsphere method) by 7.8 + 1.8 ml/min/100 gm from a baseline of 23.5 + 1.3 ml/min/100 gm. Synthetic ANF did not significantly affect the total peripheral resistance (TPR) measured at the end of the 20-minute infusion. Sodium nitroprusside (SNP), infused at an equihypotensive dose of 20 μg/kg/min i.v., produced the same hemodynamic profile in seven other animals; in contrast, 0.3 mg/ kg i.v. of hydralazine (n=7) lowered MAP by 56 + 6 mm Hg and reduced TPR index by 3.0 + 0.6 mm Hg/ml/min/100 gm, but did not change CO. Other than an increase in coronary blood flow during SNF infusion, there were no significant changes in the distribution of cardiac output. Infusion of the saline vehicle had no significant effects on any of these parameters. The results of the second experiment in anesthetized rats confirmed that hypotensive doses of 40 and 100 pmole/kg/min i.v. lowered CO (dye dilution method) from a baseline of 33 + 6 to a minimum of 24 + 2 ml/min/100 gm (p<0.05) without affecting TPR. In addition, synthetic ANF did not significantly affect heart rate (HR) but it slightly reduced cardiac contractility (dP/dt 50). These results suggest that the hypotensive dose of synthetic ANF reduced cardiac output, partially by diminishing stroke volume, and perhaps contractility.