Facilitation of reflex bradycardia does not contribute to the enhanced hypotensive effect of clonidine in aortic barodenervated rats.
Our previous studies showed that the hypotensive effect of clonidine is enhanced in rats with surgically eliminated aortic baroafferents. In this study, we investigated whether this effect of clonidine is related to facilitation of baroreceptor control of reflex bradycardia. The effects of clonidine on blood pressure (BP), heart rate (HR), and baroreflex-mediated decreases in HR (baroreflex sensitivity, BRS) were studied in conscious aortic barodenervated (ABD) and sham-operated (SO) rats. The slope of the baroreflex curve relating increments in mean arterial pressure (MAP) induced by phenylephrine to corresponding baroreflex-mediated bradycardic responses was taken as an index of BRS. ABD but not the sham operation caused immediate and significant (p < 0.05) increases in BP and HR and an impairment of BRS. Two days after ABD, these parameters, except the BRS, subsided to near control levels. Starting from similar baseline values of BP and HR, clonidine (30 microg/kg, i.v.) elicited significantly (p < 0.05) greater decreases in MAP in conscious ABD rats compared with SO rats (-23 +/- 2 mm Hg vs. -7 +/- 2 mm Hg). The enhanced hypotensive effect of clonidine in ABD rats was associated with a significant reduction in baroreceptor-mediated reflex bradycardic responses to increments in BP evoked by phenylephrine. The slope of the baroreflex curves that represented the BRS showed approximately 40% reduction after treatment with clonidine (baseline BRS, -1.2 +/- 0.06 beats/min/mm Hg; clonidine, -0.73 +/- 0.07 beats/min/mm Hg). On the other hand, a threefold lower decrease in BP by clonidine in SO rats was not associated with any alteration in BRS. These findings support the hypothesis that aortic baroreceptors exert a tonically active restraining influence on centrally mediated hypotension. More important, the results do not favor a role for facilitation of baroreflexes in the enhanced hypotensive effect of clonidine in denervated rats.
El-Mas
M M
MM
Department of Pharmacology, Faculty of Pharmacy, University of Alexandria, Egypt.
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects* / Q000294:innervation; D017704:Baroreflex; D001794:Blood Pressure / Q000187:drug effects; D001919:Bradycardia / Q000503:physiopathology*; D003000:Clonidine / Q000494:pharmacology*; D003714:Denervation; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000959:Antihypertensive Agents; D003000:Clonidine