title: Global- and renal-specific sympathoinhibition in aldosterone hypertension.
abstract: Recent technology for chronic electric activation of the carotid baroreflex and renal nerve ablation provide global and renal-specific suppression of sympathetic activity, respectively, but the conditions for favorable antihypertensive responses in resistant hypertension are unclear. Because inappropriately high plasma levels of aldosterone are prevalent in these patients, we investigated the effects of baroreflex activation and surgical renal denervation in dogs with hypertension induced by chronic infusion of aldosterone (12 μg/kg per day). Under control conditions, basal values for mean arterial pressure and plasma norepinephrine concentration were 100±3 mm Hg and 134±26 pg/mL, respectively. By day 7 of baroreflex activation, plasma norepinephrine was reduced by ≈40% and arterial pressure by 16±2 mm Hg. All values returned to control levels during the recovery period. Arterial pressure increased to 122±5 mm Hg concomitant with a rise in plasma aldosterone concentration from 4.3±0.4 to 70.0±6.4 ng/dL after 14 days of aldosterone infusion, with no significant effect on plasma norepinephrine. After 7 days of baroreflex activation at control stimulation parameters, the reduction in plasma norepinephrine was similar but the fall in arterial pressure (7±1 mm Hg) was diminished (≈55%) during aldosterone hypertension when compared with control conditions. Despite sustained suppression of sympathetic activity, baroreflex activation did not have central actions to inhibit either the stimulation of vasopressin secretion or drinking induced by increased plasma osmolality during chronic aldosterone infusion. Finally, renal denervation did not attenuate aldosterone hypertension. These findings suggest that aldosterone excess may portend diminished blood pressure lowering to global and especially renal-specific sympathoinhibition during device-based therapy.
authors.affiliation: From the Department of Physiology and Biophysics (T.E.L., B.L., D.A.H.) and Department of Surgery (D.A.H.), University of Mississippi Medical Center, Jackson; CVRx, Inc., Minneapolis, MN (A.W.C., D.G.); and North Memorial Medical Center, Trauma Services, Robbinsdale, MN (E.D.I.). tlohmeier@umc.edu.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Lohmeier
authors.affiliation: From the Department of Physiology and Biophysics (T.E.L., B.L., D.A.H.) and Department of Surgery (D.A.H.), University of Mississippi Medical Center, Jackson; CVRx, Inc., Minneapolis, MN (A.W.C., D.G.); and North Memorial Medical Center, Trauma Services, Robbinsdale, MN (E.D.I.).
authors.forename: Boshen
authors.initials: B
authors.lastname: Liu
authors.affiliation: From the Department of Physiology and Biophysics (T.E.L., B.L., D.A.H.) and Department of Surgery (D.A.H.), University of Mississippi Medical Center, Jackson; CVRx, Inc., Minneapolis, MN (A.W.C., D.G.); and North Memorial Medical Center, Trauma Services, Robbinsdale, MN (E.D.I.).
authors.forename: Drew A
authors.initials: DA
authors.lastname: Hildebrandt
authors.affiliation: From the Department of Physiology and Biophysics (T.E.L., B.L., D.A.H.) and Department of Surgery (D.A.H.), University of Mississippi Medical Center, Jackson; CVRx, Inc., Minneapolis, MN (A.W.C., D.G.); and North Memorial Medical Center, Trauma Services, Robbinsdale, MN (E.D.I.).
authors.forename: Adam W
authors.initials: AW
authors.lastname: Cates
authors.affiliation: From the Department of Physiology and Biophysics (T.E.L., B.L., D.A.H.) and Department of Surgery (D.A.H.), University of Mississippi Medical Center, Jackson; CVRx, Inc., Minneapolis, MN (A.W.C., D.G.); and North Memorial Medical Center, Trauma Services, Robbinsdale, MN (E.D.I.).
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Georgakopoulos
authors.affiliation: From the Department of Physiology and Biophysics (T.E.L., B.L., D.A.H.) and Department of Surgery (D.A.H.), University of Mississippi Medical Center, Jackson; CVRx, Inc., Minneapolis, MN (A.W.C., D.G.); and North Memorial Medical Center, Trauma Services, Robbinsdale, MN (E.D.I.).
authors.forename: Eric D
authors.initials: ED
authors.lastname: Irwin
mesh_terms: D000450:Aldosterone / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000502:physiology; D004195:Disease Models, Animal; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology / Q000601:surgery*; D016014:Linear Models; D008297:Male; D009638:Norepinephrine / Q000097:blood*; D011897:Random Allocation; D012016:Reference Values; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects*; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D013562:Sympathectomy / Q000379:methods
chemical_list: D000450:Aldosterone; D012083:Renin; D009638:Norepinephrine
keywords: aldosterone; arterial pressure; baroreflex; sympathetic nervous system; vasopressin, kidney