Abstract
Our previous attempts to investigate the long-term hemodynamic interaction between ethanol and clonidine in telemetered spontaneously hypertensive rats (SHRs) were hampered by the lack of a sustained hypotensive response to continuous clonidine exposure. This limitation was circumvented when we adopted a limited-access clonidine (8:30 AM–4:30 PM) paradigm in a recent study. The latter paradigm was employed here to evaluate the ethanol-clonidine interaction and possible roles of myocardial function and autonomic control in this interaction. Changes in blood pressure (BP), heart rate, maximum rate of rise in BP wave (+dP/dtmax), and spectral cardiovascular autonomic profiles were measured by radiotelemetry in pair-fed SHRs receiving clonidine (150 μg/kg/day), ethanol [2.5% (w/v)], or their combination during the day for 12 weeks. Ethanol or clonidine elicited long-term decreases in BP, and their combination caused additive hypotensive response. Significant reductions in +dP/dtmax were observed upon concurrent treatment with ethanol and clonidine, in contrast to no effect for individual treatment. In addition, the combined treatment increased the high-frequency (HF) spectral band of interbeat interval (IBI-HFnu, 0.75–3 Hz) and decreased low-frequency (IBI-LFnu, 0.2–0.75 Hz) bands and IBILF/HF ratios. Clonidine-evoked reductions in plasma and urine norepinephrine and BP-LF spectral power (measure of vasomotor sympathetic tone) were not affected by ethanol. In conclusion, concurrent treatment with ethanol and clonidine shifts the sympathovagal balance toward parasympathetic dominance and elicits exaggerated hypotension as a result of a reduction in cardiac contractile force.
Footnotes
↵1 Permanent affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Alexandria, Alexandria, Egypt.
This work was supported by the National Institutes of Health National Institute on Alcohol Abuse and Alcoholism [Grant AA07839].
Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
doi:10.1124/jpet.110.173443.
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ABBREVIATIONS:
- SHRs
- spontaneously hypertensive rats
- BP
- blood pressure
- SBP
- systolic blood pressure
- DBP
- diastolic blood pressure
- HR
- heart rate
- IBI
- interbeat intervals
- FFT
- fast Fourier transformations
- LF
- low frequency
- HF
- high frequency.
- Received August 3, 2010.
- Accepted September 22, 2010.
- Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics
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