title: Prolonged activation of the baroreflex decreases arterial pressure even during chronic adrenergic blockade.
abstract: Previous studies suggest that prolonged electric activation of the baroreflex may reduce arterial pressure more than chronic blockade of alpha(1)- and beta(1,2)-adrenergic receptors. To determine whether central inhibition of sympathetic outflow has appreciable effects to chronically reduce arterial pressure by actions distinct from well-established mechanisms, we hypothesized that chronic baroreflex activation would lower arterial pressure substantially even during complete alpha(1)- and beta(1,2)-adrenergic receptor blockade. This hypothesis was tested in 6 dogs during adrenergic blockade (AB; 18 days) with and without electric activation of the carotid baroreflex (7 days). During chronic AB alone, there was a sustained decrease in the mean arterial pressure of 21+/-2 mm Hg (control: 95+/-4 mm Hg) and an approximately 3-fold increase in plasma norepinephrine concentration (control: 138+/-6 pg/mL), likely attributed to baroreceptor unloading. In comparison, during AB plus prolonged baroreflex activation, plasma norepinephrine concentration decreased to control levels, and mean arterial pressure fell an additional 10+/-1 mm Hg. Because of differences in plasma norepinephrine concentration, we also tested the acute blood pressure-lowering effects of MK-467, a peripherally acting alpha(2)-antagonist. After administration of MK-467, there was a significantly greater fall in arterial pressure during AB (15+/-3 mm Hg) than during AB plus prolonged baroreflex activation (7+/-3 mm Hg). These findings suggest that reflex-induced increases in sympathetic activity attenuate reductions in arterial pressure during chronic AB and that inhibition of central sympathetic outflow by prolonged baroreflex activation lowers arterial pressure further by previously undefined mechanisms, possibly by diminishing attendant activation of postjunctional alpha(2)-adrenergic receptors.
authors.affiliation: Department of Physiology, University of Mississippi Medical Center, 2500 North State St, Jackson, MS 39216-4505, USA. tlohmeier@physiology.umsmed.edu
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Lohmeier
authors.forename: Drew A
authors.initials: DA
authors.lastname: Hildebrandt
authors.forename: Terry M
authors.initials: TM
authors.lastname: Dwyer
authors.forename: Radu
authors.initials: R
authors.lastname: Iliescu
authors.forename: Eric D
authors.initials: ED
authors.lastname: Irwin
authors.forename: Adam W
authors.initials: AW
authors.lastname: Cates
authors.forename: Martin A
authors.initials: MA
authors.lastname: Rossing
mesh_terms: D018674:Adrenergic Antagonists / Q000494:pharmacology*; D000818:Animals; D017704:Baroreflex / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects*; D001798:Blood Proteins / Q000032:analysis; D004285:Dogs; D004573:Electrolytes / Q000652:urine; D006339:Heart Rate / Q000187:drug effects; D006400:Hematocrit; D009638:Norepinephrine / Q000097:blood; D011807:Quinolizines / Q000494:pharmacology
chemical_list: D018674:Adrenergic Antagonists; D001798:Blood Proteins; D004573:Electrolytes; D011807:Quinolizines; C055732:vatinoxan; D009638:Norepinephrine