title: Increased coronary vascular resistance cannot be reduced by inhibiting sympathetic overactivity in hypertension.
abstract: The aim of this study was to test whether increased coronary vascular resistance in hypertensive subjects can be reduced by centrally inhibiting sympathetic overactivity with dexamethasone. Coronary vascular resistance was quantitated in 11 men with untreated mild essential hypertension (RR 149 +/- 13/98 +/- 10 mm Hg) and 23 healthy, normotensive, otherwise matched men using positron emission tomography and [(15)O]H(2)O. The measurements were performed at baseline and during adenosine stimulation. Each subject was studied twice, with and without previous dexamethasone treatment for two days (0.5 mg x 4 per day). Before dexamethasone treatment, cardiac index and plasma norepinephrine concentration (1.9 +/- 0.6 vs. 1.3 +/- 0.5 nmol/l, p < 0.01) were significantly higher in hypertensive than in normotensive subjects. Additionally, both baseline and hyperemic coronary vascular resistances were higher in hypertensive than normotensive subjects (147 +/- 31 vs. 113 +/- 24 and 36 +/- 9 vs. 25 +/- 10 mm Hg.min.g.ml(-1); p < 0.05). Dexamethasone treatment significantly decreased plasma norepinephrine concentrations in hypertensive subjects, leading to comparable plasma norepinephrine concentrations in hypertensive and normotensive subjects (1.4 +/- 0.5 vs. 1.2 +/- 0.4 nmol/l; NS). However, coronary vascular resistances remained increased in hypertensive subjects. In conclusion, hypertensive subjects are characterized by sympathetic overactivity, which can be normalized by dexamethasone. However, coronary vascular resistances remained increased in hypertensive subjects after dexamethasone treatment, suggesting that other mechanisms than sympathetic overactivity-induced vasoconstriction explain the increased coronary vascular resistance in hypertension.
authors.affiliation: Turku PET Centre, Turku University, Turku, Finland. jan.sundell@utu.fi
authors.forename: Jan
authors.initials: J
authors.lastname: Sundell
authors.forename: Hanna
authors.initials: H
authors.lastname: Laine
authors.forename: Matti
authors.initials: M
authors.lastname: Luotolahti
authors.forename: Pirjo
authors.initials: P
authors.lastname: Nuutila
authors.forename: Juhani
authors.initials: J
authors.lastname: Knuuti
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D003907:Dexamethasone / Q000627:therapeutic use*; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006439:Hemodynamics; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009638:Norepinephrine / Q000097:blood; D014055:Tomography, Emission-Computed; D014655:Vascular Resistance / Q000187:drug effects*
chemical_list: D001786:Blood Glucose; D005938:Glucocorticoids; D003907:Dexamethasone; D006854:Hydrocortisone; D009638:Norepinephrine