Blood pressure and renal responses to synthetic rat atrial natriuretic factor in deoxycorticosterone acetate-salt hypertension.

To assess possible roles of atrial natriuretic factor (ANF) in the regulation of blood pressure in deoxycorticosterone acetate (DOCA)-salt hypertensive rats, we performed two series of experiments. First, we studied acute hypotensive, and natriuretic and diuretic effects of ANF in pentobarbital-anesthetized DOCA-salt hypertensive rats and age-matched controls. A synthetic rat ANF was intravenously administered as a bolus at doses of 0.5, 2.5 and 5.0 micrograms/kg. In DOCA-salt rats, a significant decrease in mean arterial pressure was observed at a dose of 5.0 micrograms/kg, whereas at a dose of 2.5 micrograms/kg in control rats. On the other hand, the diuretic and natriuretic effects of ANF were observed at a dose of 2.5 micrograms/kg in DOCA-salt rats and 5.0 micrograms/kg in control rats. Second, we examined chronic effect of ANF on the development of hypertension in DOCA-salt rats. The DOCA-salt rats, given 1% NaCl solution for drinking, were continuously infused with ANF (15, 75 and 150 micrograms/kg/day) or vehicle (physiological saline) into the jugular vein by osmotic minipumps for up to 14 days. In DOCA-salt treated rats, ANF at doses of 75 and 150 micrograms/kg/day attenuated significantly the development of hypertension, although at a dose of 15 micrograms/kg/day did not. The hypotensive effect of ANF was sustained throughout the experimental period and the effect of ANF at a dose of 150 micrograms/kg/day was more prominent than that of this peptide at a dose of 75 micrograms/kg/day. ANF did not induce any significant changes in urine volume, fluid intake and urinary excretion of sodium and potassium in DOCA-salt rats when compared to those in vehicle-infused DOCA-salt rats. These results indicate that DOCA-salt rats are more sensitive to ANF in diuretic and natriuretic effects, and less sensitive to ANF in hypotensive effect compared to control rats. Moreover, it is suggested that ANF can affect the regulation of blood pressure by its vascular effect in the development of hypertension in DOCA-salt rats.