Hemodynamic stress activates locus coeruleus neurons of unanesthetized rats

The effects of hypotensive stress elicited by nitroprusside infusion on discharge activity of noradrenergic locus coeruleus (LC) neurons of unanesthetized rats were characterized. Nitroprusside (75 micrograms/30 microliters/min, 15 min IV infusion) decreased mean arterial pressure of unanesthetized rats by 50 +/- 2 mmHg (n = 5). Simultaneous recordings of LC spontaneous discharge revealed an increase in discharge rate (197 +/- 87%) that was associated with hypotension. A lower concentration of nitroprusside (10 micrograms/30 microliters/min) that decreased blood pressure of halothane-anesthetized rats by 55 +/- 2 mmHg was much less effective in producing hypotension and did not increase LC discharge when administered to unanesthetized rats. Prior administration of the CRF antagonist, alpha helical CRF9-41 (50 micrograms, ICV) greatly attenuated LC activation by nitroprusside. These findings demonstrate that LC activation elicited by nitroprusside is dependent on the magnitude of hypotension. The present results also demonstrate that nitroprusside is a less potent hemodynamic challenge in unanesthetized rats. Finally, LC activation associated with nitroprusside administration to unanesthetized rats is mediated to a large extent by CRF, confirming findings in anesthetized rats.