We investigated the role of central endothelin-A (ET_A) receptors and nitric oxide (NO) in regulating arterial pressure during restraint stress and recovery from stress. Rats received intracerebroventricular (icv) injections of the ET_A receptor antagonist BQ123 (24 µg/kg) and were then subjected to two restraint-rest cycles (1 h of restraint and 1 h of rest/cycle). Although mean arterial pressure (MAP) values in BQ123-treated and control rats increased at the onset of restraint and remained elevated during restraint, MAP values in BQ123-treated rats were consistently greater than in control rats. During rest periods, MAP values in control rats decreased to below baseline levels, whereas those in BQ123-treated rats remained significantly higher. NO content was decreased in the brain stems of BQ123-treated compared with control rats after the 4-h protocol. Injections (icv) of the NO synthase (NOS) inhibitor N^G-nitro-L-arginine (L-NNA) eliminated the decreases in MAP values during rest periods in both BQ123-treated and control rats. Inhibition of neuronal NOS with icv injection of 7-nitroindazole sodium salt resulted in MAP values intermediate between control rats and rats receiving L-NNA. These results support the hypothesis that endothelin acts through ET_A receptors in the brain, possibly via release of NO, to decrease arterial pressure during restraint and recovery from restraint.