Blood pressure and renal responses to synthetic rat atrial natriuretic factor (ANF) in spontaneously hypertensive rats (SHR)

To assess the possible roles of atrial natriuretic factor (ANF) in the regulation of blood pressure in spontaneously hypertensive rats (SHR), we performed two series of experiments. Firstly, we studied hypotensive, natriuretic and diuretic effects of ANF in pentobarbital-anesthetized adult SHR and age-matched Wistar-Kyoto rats (WKY)9 A synthetic ANF of 25 amino acid residues was intravenously administered as a bolus in doses of 0.1 μg/kg, 1.0 μg/kg, 2.5 μg/kg and 5.0 μg/kg. In SHR, a significant decrease in mean arterial pressure (MAP) was observed at the dose of 1.0 ptg/kg, and MAP decreased in a dose-dependent manner. On the other hand, in WKY group, the decrease in MAP was observed at the dose of 5.0 μg/kg. The diuretic and natriuretic effects of ANF were observed at the dose of 2.5 μg/kg in SHR and 5.0μg/kg in WKY. Secondly, we also studied chronic effect of ANF on the development of hypertension in 6-week-old SHR. The SHR, on regular diet or given 1% NaCl solution for drinking, were continuously infused into the jugular vein by osmotic minipumps with ANF (150 μg/kg/day) or vehicle (physiological saline) as controls for up to 14 days. ANF attenuated transiently the development of hypertension in the sodiumloaded SHR. But the blood pressure returned to control levels by day 5. In SHR on regular diet, ANF did not affect the development of hypertension. In addition, ANF did not induce any significant changes in urine volume, fluid intake, urinary sodium, potassium and kallkrein excretion in SHR on both sodium conditions 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, they suggest that ANF may exert some roles by its vascular effect at the early stage of development of hypertension in SHR on sodium loading.