Angiotensin II stimulates sympathetic output by a direct spinal action

When administered intrathecally in a dose of 10 mu to the ninth thoracic segment of the spinal cord in the anesthetized rat, angiotensin II produced a transient increase in systolic and diastolic arterial pressures lasting 1-4 min. Heart rate was also increased, but in this case for more than 30 min. Similar administration of 5 micrograms or of CSF had no effect on either arterial pressure or heart rate. Neither the arterial pressure nor the heart rate response to 10 micrograms of angiotensin II was observed in rats given hexamethonium (10 mg/kg, i.v.), suggesting that the effects were mediated by spinal activation of sympathetic output. When the rats were pretreated with 10 micrograms of [Sar1, IIe8]-angiotensin II three min prior to angiotensin II, there was a block of the increase in arterial pressure but not of the increase in heart rate. When the antagonist was given 15 min prior to angiotensin II, the full pressor response appeared, suggesting that the antagonist was effective for less than 15 min; in addition, after the antagonist alone, while arterial pressure remained unaltered, there was a gradual increase in heart rate suggesting that the analogue had agonistic effects on mechanisms regulating heart rate. These results suggest that angiotensin II activates sympathetic mechanisms by a spinal action and that arterial pressure and heart rate are regulated differentially, arterial pressure via a mechanism which is antagonized by [Sar1, IIe8]-angiotensin II, and heart rate via a mechanism in which the analog can act as an agonist.