Effects of chronic ethanol feeding on clonidine-evoked reductions in blood pressure, heart rate, and their variability: time-domain analyses.
The effects of chronic ethanol administration on the acute hemodynamic effects of clonidine were investigated in conscious radiotelemetered spontaneously hypertensive rats (SHRs). Changes evoked by clonidine (30 micro g/kg i.p.) in blood pressure, heart rate, and their variability were evaluated in ethanol [2.5 or 5% (w/v), 12 weeks] and pair-fed control rats. The blood pressure variability was determined as the standard deviation of the mean arterial pressure (SDMAP). Two heart rate variability indices were used, the standard deviation of beat-to-beat intervals (SDRR) and the root mean square of successive beat-to-beat differences in R-R interval durations (rMSSD). Compared with control rats, ethanol (2.5 and 5%)-fed rats exhibited concentration-related reductions in mean arterial pressure (MAP) and SDMAP versus no change in heart rate variability. In control rats, clonidine caused a significant reduction in MAP that continued for at least 5 h and was associated with significant reductions in SDMAP, SDRR, and rMSSD, responses that are consistent with the inhibition of central sympathetic tone. The hypotensive effect of clonidine was attenuated by ethanol in a concentration-related manner. The maximum reductions in MAP elicited by clonidine in ethanol (2.5 and 5%)-fed rats amounted to -23.4 +/- 2.8 and -15.1 +/- 1.5 mm Hg, respectively, compared with -35.4 +/- 1.2 mm Hg in control rats. The clonidine-induced reductions in SDMAP, SDRR, and rMSSD were also significantly attenuated by ethanol. These findings suggest that the attenuation of MAP and heart rate variability responses elicited by clonidine in ethanol-fed SHRs reflects alterations in the sympathovagal balance, which may be implicated in the antagonistic hemodynamic interaction between the two drugs.
El-Mas
Mahmoud M
MM
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858, USA.
Abdel-Rahman
Abdel A
AA
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology*; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D013997:Time Factors
D000959:Antihypertensive Agents; D002492:Central Nervous System Depressants; D000431:Ethanol; D003000:Clonidine