Atrial natriuretic factor inhibits the hypertension induced by chronic infusion of norepinephrine in conscious rats

To assess the physiological role of atrial natriuretic factors in the regulation of blood pressure and sodium-water excretion, we studied the chronic effects of continuous infusion of a synthetic atrial natriuretic factor of 25 amino acids for up to 3 days on systolic blood pressure, urine volume, and urinary excretion of sodium, prostaglandin E₂ and kallikrein in conscious rats, and also evaluated the antihypertensive effect of this substance in rats with hypertension caused by chronic infusion of norepinephrine. Continuous infusion of atrial natriuretic factor (150 μg/kg per day) into the jugular vein via osmotic minipumps did not induce any changes in systolic blood pressure, urine volume, and urinary excretion of sodium, prostaglandin E₂, and kallikrein for up to 3 days, compared with those in vehicle-infused rats. When the same dose of atrial natriuretic factor was administered simultaneously with 1.8 mg/kg per day of norepinephrine infused intraperitoneally by osmotic minipumps, the systolic blood pressure of conscious rats rose on day 1 to only 127.3 ± 6.3 mm Hg compared with the rise to 146.3 ± 1.6 mm Hg when norepinephrine alone was infused (P < 0.05). The antihypertensive effect of atrial natriuretic factor was sustained for 3 days in rats infused with norepinephrine. The administration of atrial natriuretic factor to rats made hypertensive by 3 days of infusion with norepinephrine alone returned the blood pressure to control levels, and the antihypertensive effect was sustained throughout the experimental period lasting for 3 days. These results indicate that a subdepressor dose of synthetic atrial natriuretic factor can modulate the vasopressor effect of norepinephrine, and may be involved in the regulation of blood pressure, independent of the renal effects of these substances.