title: Dietary Ca2+ prevents NaCl-sensitive hypertension in spontaneously hypertensive rats by a sympatholytic mechanism.
abstract: The current study tested the hypothesis that dietary Ca2+ supplementation reverses the NaCl-sensitive component of hypertension and the associated neurochemical abnormalities in the NaCl-sensitive spontaneously hypertensive rat (SHR-S). Male SHR-S were begun on one of four diets at 8 weeks of age: control (0.75% NaCl/0.68% Ca2+); high NaCl (8.00% NaCl/0.68% Ca2+); high Ca2+ (0.75% NaCl/2.00% Ca2+); and high NaCl/high Ca2+ (8.00% NaCl/2.00% Ca2+). High NaCl SHR-S (X2 weeks) had higher mean arterial pressure (MAP) (161 +/- 4 mm Hg) than controls (149 +/- 3 mm Hg; P less than .05). Supplementation with Ca2+ prevented the rise in MAP in high NaCl rats, but did not alter MAP in controls. The 8% NaCl diet elevated plasma norepinephrine and reduced anterior hypothalamic (AHA) norepinephrine stores and turnover; concomitant Ca2+ supplementation restored both plasma norepinephrine and AHA norepinephrine turnover to normal. Clonidine was microinjected into the AHA of rats maintained on the four diets for 2 weeks to test the hypothesis that dietary Ca2+ supplementation prevents the previously observed NaCl-induced upregulation of alpha 2-adrenoceptors in AHA. Clonidine caused dose-dependent decreases in MAP that were greater in high NaCl rats than in controls. The Ca2+ supplementation prevented the exaggerated depressor response to clonidine in the high NaCl group, but not in the controls. The Ca2+ supplementation had no effect on pretreatment MAP or on MAP responses to clonidine in control NaCl-resistant SHR (SHR-R) or Wistar-Kyoto (WKY) rats. Thus, dietary Ca2+ supplementation prevents the NaCl-induced exacerbation of hypertension and augmented depressor response to clonidine in SHR-S by increasing noradrenergic input to AHA, thereby preventing the upregulation of AHA alpha 2-adrenoceptors.
authors.affiliation: Department of Medicine, University of Alabama, Birmingham 35294.
authors.forename: S
authors.initials: S
authors.lastname: Oparil
authors.forename: J M
authors.initials: JM
authors.lastname: Wyss
authors.forename: R H
authors.initials: RH
authors.lastname: Yang
authors.forename: H K
authors.initials: HK
authors.lastname: Jin
authors.forename: Y F
authors.initials: YF
authors.lastname: Chen
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002136:Calcium, Dietary / Q000008:administration & dosage*; D003000:Clonidine / Q000494:pharmacology; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D007031:Hypothalamus / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology; D012965:Sodium Chloride / Q000494:pharmacology
chemical_list: D002136:Calcium, Dietary; D011942:Receptors, Adrenergic, alpha; D012965:Sodium Chloride; D003000:Clonidine; D009638:Norepinephrine