Chronic ethanol-clonidine hemodynamic interaction in telemetered spontaneously hypertensive rats.
Our previous studies have established that ethanol, administered acutely or chronically, attenuates the hypotensive action of the centrally acting drug clonidine. In this study, we employed the radiotelemetry technique to evaluate the long-term hemodynamic interaction between the two drugs administered simultaneously to spontaneously hypertensive rats (SHRs). Changes in blood pressure (BP), heart rate (HR), and their variability was determined in pair-fed rats receiving ethanol (5%, w/v), clonidine pellets (10 mg/pellet, s.c.), or their combination for 28 days. Ethanol feeding caused significant decreases and increases in BP and HR, respectively. The time-domain variability indices of BP and HR were also reduced by ethanol. Clonidine produced significant reductions in BP and HR that were evident for only 1-2 days and disappeared thereafter. In rats receiving the combined ethanol and clonidine treatment, hemodynamic changes were identical to those produced by ethanol alone. These findings suggest (i) long-term exposure of SHRs to moderate amounts of ethanol reduces HR variability, possibly due to diminished cardiac vagal modulation, and (ii) the lack of a maintained hypotensive response to clonidine, administered via timed-release pellets, made the evaluation of its chronic interaction with ethanol unfeasible.
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; D001919:Bradycardia / Q000139:chemically induced; D003000:Clonidine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004343:Drug Implants; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D000431:Ethanol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006439:Hemodynamics / Q000187:drug effects*; D007022:Hypotension / Q000139:chemically induced; D007279:Injections, Subcutaneous; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D013686:Telemetry / Q000295:instrumentation / Q000379:methods*; D013997:Time Factors; D016896:Treatment Outcome
D003692:Delayed-Action Preparations; D004343:Drug Implants; D000431:Ethanol; D003000:Clonidine