Contrasting effects of chronic ethanol feeding on centrally and peripherally evoked hypotension in telemetered female rats.
Our previous studies have shown that ethanol compromises hypotension produced by centrally acting antihypertensive agents in normotensive and hypertensive male rats. The present study investigated whether female rats are as susceptible as male rats to the deleterious effect of ethanol on centrally evoked hypotension. The study was extended to investigate ethanol effects on the time-domain indices of variability in blood pressure [standard deviation of mean arterial pressure (SDMAP)] and heart rate [standard deviation of beat-to-beat intervals (SDRR) and root mean square of successive differences in R-R intervals (rMSSD)]. The hemodynamic effects of a single intraperitoneal dose of clonidine (30 microg/kg) were evaluated in radiotelemetered ethanol-fed (5%, 12 weeks) and pair-fed control Sprague-Dawley rats. In control rats, clonidine caused a significant reduction in MAP that continued for at least 6 h and was associated with reductions in SDMAP and SDRR but not rMSSD, suggesting inhibition of central sympathetic tone. A maximum hypotensive response of -16.4+/-1.7 mm Hg was demonstrated 40 min after clonidine administration. Ethanol feeding significantly attenuated clonidine hypotension whereas it potentiated the associated reduction in SDMAP. To verify the selectivity of ethanol-clonidine interaction, the effects of ethanol on peripherally mediated hemodynamic responses to hydralazine (0.5 mg/kg ip) were investigated. In contrast to its antagonistic effect on clonidine hypotension, ethanol significantly potentiated the hypotensive effect of hydralazine. Together, these findings demonstrate that chronic ethanol feeding exerts opposite effects on centrally (attenuation) and peripherally (potentiation) evoked hypotension in female rats. The interaction of ethanol with antihypertensive agents may not be related to changes in hemodynamic variability.
El-Mas
Mahmoud M
MM
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858, USA.
Abdel-Rahman
Abdel A
AA
D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003000:Clonidine / Q000494:pharmacology; D004334:Drug Administration Schedule; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007022:Hypotension / Q000139:chemically induced / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013686:Telemetry / Q000379:methods*
D000431:Ethanol; D003000:Clonidine