title: Differential modulation by estrogen of alpha2-adrenergic and I1-imidazoline receptor-mediated hypotension in female rats.
abstract: We have recently shown that estrogen negatively modulates the hypotensive effect of clonidine (mixed alpha2-/I1-receptor agonist) in female rats and implicates the cardiovascular autonomic control in this interaction. The present study investigated whether this effect of estrogen involves interaction with alpha2- and/or I1-receptors. Changes evoked by a single intraperitoneal injection of rilmenidine (600 microg/kg) or alpha-methyldopa (100 mg/kg), selective I1- and alpha2-receptor agonists, respectively, in blood pressure, hemodynamic variability, and locomotor activity were assessed in radiotelemetered sham-operated and ovariectomized (Ovx) Sprague-Dawley female rats with or without 12-wk estrogen replacement. Three time domain indexes of hemodynamic variability were employed: the standard deviation of mean arterial pressure as a measure of blood pressure variability and the standard deviation of beat-to-beat intervals (SDRR) and the root mean square of successive differences in R-wave-to-R-wave intervals as measures of heart rate variability. In sham-operated rats, rilmenidine or alpha-methyldopa elicited similar hypotension that lasted at least 5 h and was associated with reductions in standard deviation of mean arterial pressure. SDRR was reduced only by alpha-methyldopa. Ovx significantly enhanced the hypotensive response to alpha-methyldopa, in contrast to no effect on rilmenidine hypotension. The enhanced alpha-methyldopa hypotension in Ovx rats was paralleled with further reduction in SDRR and a reduced locomotor activity. Estrogen replacement (17beta-estradiol subcutaneous pellet, 14.2 microg/day, 12 wk) of Ovx rats restored the hemodynamic and locomotor effects of alpha-methyldopa to sham-operated levels. These findings suggest that estrogen downregulates alpha2- but not I1-receptor-mediated hypotension and highlight a role for the cardiac autonomic control in alpha-methyldopa-estrogen interaction.
authors.affiliation: Dept. of Pharmacology, School of Medicine, East Carolina Univ., Greenville, NC 27858, 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: D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D004967:Estrogens / Q000008:administration & dosage*; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D020249:Hormone Replacement Therapy / Q000379:methods; D007022:Hypotension / Q000139:chemically induced / Q000378:metabolism*; D054755:Imidazoline Receptors; D008750:Methyldopa / Q000008:administration & dosage*; D010080:Oxazoles / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077769:Rilmenidine
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D004967:Estrogens; D054755:Imidazoline Receptors; D010080:Oxazoles; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug; C410887:imidazoline I1 receptors; D008750:Methyldopa; D000077769:Rilmenidine