Acute and chronic effects of synthetic atrial natriuretic factor on blood pressure and sodium excretion in spontaneously hypertensive rats.

To assess possible roles of atrial natriuretic factor (ANF) in the regulation of blood pressure in spontaneously hypertensive rats (SHR), we performed two series of experiments. First, we studied acute hypotensive, natriuretic and diuretic effects of ANF in pentobarbital-anesthetized SHR and age-matched Wistar-Kyoto rats (WKY). A synthetic ANF of 25 amino acid residues was intravenously administered as a bolus at doses of 0.1, 1.0, 2.5 and 5.0 micrograms/kg. In SHR group, a significant decrease in mean arterial pressure (MAP) was observed at a dose of 1.0 micrograms/kg, and the decrease was dose-dependent. On the other hand, in WKY group, the hypotensive effect of ANF was not observed until a dose of 5.0 micrograms/kg. The diuretic and natriuretic effects of ANF were observed at a dose of 2.5 micrograms/kg in SHR and 5.0 micrograms/kg in WKY, respectively. Second, we also studied chronic effect of ANF on the development of hypertension in 6-week-old SHR. The SHRs, on regular diet or given 1% NaCl solution for drinking, were continuously infused into the jugular vein by osmotic minipumps with ANF (15, 75 and 150 micrograms/kg/day) or vehicle (physiological saline) as controls for up to 14 days. ANF at a dose of 150 micrograms/kg/day attenuated transiently the development of hypertension in the sodium-loaded SHR. However, the blood pressure returned to control levels by day 5. ANF at doses of 15 and 75 micrograms/kg/day did not affect the development of hypertension. In SHR on regular diet, ANF at a dose of 150 micrograms/kg/day did not affect the development of hypertension. In addition, ANF did not induce any significant changes in urine volume, fluid intake, and urinary excretion of sodium and potassium in SHR, whether they were sodium-loaded or not, when compared to those in vehicle-infused SHR. These results indicate that there may be a significant difference in the sensitivity to diuretic, natriuretic and hypotensive actions of ANF between SHR and WKY. Moreover, it is suggested that ANF may play significant roles by its vascular effect at the early stage of development of hypertension in sodium-loaded SHR.(ABSTRACT TRUNCATED AT 250 WORDS)