Centrally mediated reduction in cardiac output elicits the enhanced hypotensive effect of clonidine in conscious aortic barodenervated rats.

In a previous study, we showed that centrally mediated hypotensive responses are enhanced in aortic barodenervated (ABD) rats as compared with sham-operated (SO) rats. In the present study, we tested the hypothesis that the high basal total peripheral resistance (TPR) of ABD rats accounts for enhanced hypotensive responses to clonidine in this rat model. Aortic barodenervation resulted in acute increases in blood pressure (BP) and heart rate (HR) in anesthetized rats, associated with significant increases in plasma norepinephrine (NE) levels and TPR; cardiac index (CI) and stroke volume (SV) were not affected. After recovery from anesthesia, conscious ABD rats had significantly increased BP at 3 h after barodenervation; BP returned to SO levels by 48 h even though plasma NE levels and TPR remained significantly increased. On the other hand, CI and SV showed significant reductions, beginning at 3 h, and remained low throughout the postdenervation period (48 h); the reduction in CI offset the increase in TRP and may therefore account for the restoration of BP of ABD rats to normal levels. Beginning at similar baseline BP values, cumulative intracisternal (i.c.) doses of clonidine (0.02-2.5 micrograms) elicited greater decreases in BP and plasma NE levels in conscious ABD as compared with SO rats. These responses were centrally mediated because systemic administration of 0.12 micrograms clonidine, a dose that elicited near maximal hypotensive response after i.c. administration, affected neither BP nor plasma NE levels. Contrary to the hypothesis, the hypotensive effect of clonidine in ABD rats resulted exclusively from a reduction in CO (owing to reductions in both HR and SV) because TPR was not affected. These findings suggest that (a) in ABD rats, a reduction in CO offsets a sustained sympathetically mediated elevation in TPR and restores BP to normal levels; and (b) an enhanced hypotensive response to clonidine in ABD as compared with SO rats cannot be accounted for by a higher basal TRP but rather by elicitation of greater reductions in CO through a centrally mediated sympathoinhibitory action.