title: Chronic ethanol administration attenuates imidazoline I1 receptor- or alpha 2-adrenoceptor-mediated reductions in blood pressure and hemodynamic variability in hypertensive rats.
abstract: Our previous studies have demonstrated that acute ethanol administration counteracts imidazoline I(1) receptor but not alpha(2)-adrenoceptor-mediated hypotension in spontaneously hypertensive rats (SHR). In the present study, we investigated the effect of chronic ethanol administration on hypotensive responses elicited by acute administration of selective imidazoline I(1) receptor (rilmenidine) or alpha(2)-adrenoceptor (alpha-methyldopa) agonist along with ethanol effects on: (i) locomotor activity and (ii) time-domain indices of variability in blood pressure (standard deviation of mean arterial pressure) and heart rate (standard deviation of beat-to-beat intervals and root mean square of successive differences in R-R intervals). Hemodynamic and locomotor responses elicited by rilmenidine or alpha-methyldopa were assessed in radiotelemetered ethanol-fed (2.5% or 5% w/v, 12 week) and control SHR. In control SHR, i.p. rilmenidine (600 microg/kg) or alpha-methyldopa (100 mg/kg) significantly reduced blood pressure. Rilmenidine had no effect on heart rate whereas alpha-methyldopa elicited a biphasic response (tachycardia followed by bradycardia). Blood pressure and heart rate oscillations were also reduced by both drugs, which may conform to sympathoinhibition. The hypotensive effect of rilmenidine or alpha-methyldopa was significantly attenuated by ethanol feeding (2.5% or 5%) in a concentration-dependent manner. In addition, ethanol attenuated alpha-methyldopa-evoked reduction in heart rate, but not blood pressure, variability in marked contrast to attenuating rilmenidine-evoked reductions in blood pressure, but not heart rate, variability. These findings demonstrate that, unlike its acute effects, chronic ethanol attenuates both imidazoline I(1) receptor and alpha(2)-adrenoceptor-mediated hypotension whereas its effect on hemodynamic variability depended on the nature of the hypotensive stimulus.
authors.affiliation: Department of Pharmacology, School of Medicine, East Carolina University, 353, Greenville, NC 27858-4353, 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: D058647:Adrenergic alpha-2 Receptor Agonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D054755:Imidazoline Receptors; D008297:Male; D008750:Methyldopa / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010080:Oxazoles / Q000494:pharmacology; D021122:Protein Subunits / Q000819:agonists / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D011955:Receptors, Drug / Q000819:agonists / Q000502:physiology*; D000077769:Rilmenidine
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D054755:Imidazoline Receptors; D010080:Oxazoles; D021122:Protein Subunits; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug; C410887:imidazoline I1 receptors; D000431:Ethanol; D008750:Methyldopa; D000077769:Rilmenidine