title: Reduced cardiac contractile force due to sympathovagal dysfunction mediates the additive hypotensive effects of limited-access regimens of ethanol and clonidine in spontaneously hypertensive rats.
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/dt(max)), 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/dt(max) 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-HF(nu), 0.75-3 Hz) and decreased low-frequency (IBI-LF(nu), 0.2-0.75 Hz) bands and IBI(LF/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.
authors.affiliation: Department of Pharmacology, School of Medicine, East Carolina University, Greenville, North Carolina 27834, USA.
authors.forename: Mahmoud M
authors.initials: MM
authors.lastname: El-Mas
authors.forename: Abdel A
authors.initials: AA
authors.lastname: Abdel-Rahman
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions / Q000502:physiology*; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology* / Q000652:urine; D005583:Fourier Analysis; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000097:blood / Q000652:urine; D051381:Rats; D011918:Rats, Inbred SHR; D013686:Telemetry; D014630:Vagus Nerve / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D000959:Antihypertensive Agents; D000431:Ethanol; D003000:Clonidine; D009638:Norepinephrine