Our previous studies showed that ethanol selectively counteracts centrally mediated hypotensive responses. In this study, we investigated the role of sympathetic nerve activity, cardiac output (CO), and total peripheral resistance (TPR) in this antagonistic hemodynamic interaction between ethanol and clonidine. Changes in blood pressure (BP), heart rate (HR), CO, stroke volume (SV), and TPR elicited by intracisternal (i.c.) clonidine and subsequent ethanol or saline were evaluated in conscious freely moving spontaneously hypertensive rats (SHRs). Clonidine (0.5 microg, i.c.) evoked hypotension was due to a significant reduction in TPR (from 3.6+/-0.21 to 2.8+/-0.17 mm Hg/ml/min/100 g), which was associated with a significant (p < 0.05) reduction in plasma norepinephrine (NE, from 660+/-115 to 310+/-50 pg/ml), measured as index of sympathetic activity. Ethanol (1 g/kg, i.v.) counteracted the hypotensive effect of clonidine and produced significant (p < 0.05) increases in plasma NE and TPR. Further support for the hypothesis that ethanol selectively counteracts centrally mediated hypotension was sought by investigating the effect of ethanol on peripherally mediated hemodynamic responses to hydralazine. Hydralazine (0.4 mg/kg, i.v.) produced a hypotension similar in magnitude to that produced by clonidine, which was also due to a significant reduction in TPR. However, unlike the case with clonidine, reflex increases in HR, SV, and hence CO were evident. Ethanol given after hydralazine produced a short-lived pressor effect (<10 min vs. 60 min in case of clonidine) in spite of a sustained increase in TPR. The latter was offset by the simultaneous decreases in CO, SV, and HR. A 30% increase in plasma NE caused by hydralazine returned to baseline level after ethanol or saline. Blood ethanol concentrations were similar in all treatment groups. These findings suggest that ethanol selectively counteracts centrally evoked hypotensive responses by counteracting the sympathoinhibition-mediated decreases in TPR elicited by centrally administered clonidine in conscious SHRs.