title: Vascular influences of calcium supplementation and vitamin D-induced hypercalcemia in NaCl-hypertensive rats.
abstract: This 8-week study investigated the effects of increasing dietary Ca2+ content from 1.0% to 3.0% and hypercalcemia induced by oral 1alpha-OH vitamin D3 (1OH-D3, 1.2 microg/kg), on arterial tone in NaCl-hypertensive rats. The high-Ca2+ diet completely prevented the increase in blood pressure induced by the 6.0% NaCl chow, while plasma total Ca2+ and body weight were not different from controls. The 1OH-D3 treatment moderately elevated plasma total Ca2+ and attenuated the NaCl-induced rise in blood pressure, but also impaired weight gain. The tone of isolated mesenteric arterial rings was examined at the end of study. The endothelium-independent relaxations to nitroprusside, isoproterenol, and cromakalim were impaired in NaCl-hypertension. Experiments with NG-nitro-l-arginine methyl ester and tetraethylammonium in vitro suggested that both the nitric oxide- and hyperpolarization-mediated components of endothelium-dependent relaxation to acetylcholine were reduced in NaCl-hypertensive rats. All of the impaired relaxations in NaCl hypertension were normalized by concomitant Ca2+ supplementation. The 1OH-D3 treatment did not affect vascular relaxation, but it attenuated maximal contractile responses induced by norepinephrine and KCl by more than 50%. The reduced vasoconstrictor responses could not be explained by increased apoptosis in the vessel wall, but calcification may have played a role, since moderate signs of medial or adventitial calcification were observed in the aortic preparations after the 1OH-D3 treatment. In conclusion, a high-Ca2+ diet, which did not cause hypercalcemia, normalized blood pressure and endothelium-dependent and endothelium-independent vasorelaxation in NaCl-hypertensive rats. In contrast, chronic hypercalcemia induced by 1OH-D3 was associated with moderately lowered blood pressure, possibly because of reduced vasoconstrictor responses in arterial smooth muscle.
authors.affiliation: Department of Pharmacological Sciences, Medical School, University of Tampere, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Kähönen
authors.forename: Satu
authors.initials: S
authors.lastname: Näppi
authors.forename: Pasi
authors.initials: P
authors.lastname: Jolma
authors.forename: Nina
authors.initials: N
authors.lastname: Hutri-Kähönen
authors.forename: Jari-Petteri
authors.initials: JP
authors.lastname: Tolvanen
authors.forename: Heikki
authors.initials: H
authors.lastname: Saha
authors.forename: Pasi
authors.initials: P
authors.lastname: Koivisto
authors.forename: Leena
authors.initials: L
authors.lastname: Krogerus
authors.forename: Jarkko
authors.initials: J
authors.lastname: Kalliovalkama
authors.forename: Ilkka
authors.initials: I
authors.lastname: Pörsti
mesh_terms: D000818:Animals; D017209:Apoptosis; D001794:Blood Pressure / Q000187:drug effects; D002136:Calcium, Dietary / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D006934:Hypercalcemia / Q000139:chemically induced*; D006973:Hypertension / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D012965:Sodium Chloride / Q000009:adverse effects*; D014664:Vasodilation / Q000187:drug effects; D014807:Vitamin D / Q000009:adverse effects*
chemical_list: D002136:Calcium, Dietary; D014807:Vitamin D; D009599:Nitroprusside; D012965:Sodium Chloride; D019331:NG-Nitroarginine Methyl Ester