title: Endothelial function in deoxycorticosterone-NaCl hypertension: effect of calcium supplementation.
abstract: BACKGROUND
  Dietary calcium intake has been suggested to correlate inversely with blood pressure in humans and experimental animals. However, the effects of calcium supplementation on hypertensive disturbances of the endothelium have not been well characterized.
  
  
  RESULTS
  Wistar-Kyoto rats made hypertensive by deoxycorticosterone (DOC)-NaCl treatment, but a concurrent increase in chow calcium content from 1.1% to 2.5% markedly attenuated the rise in blood pressure. The function of isolated mesenteric arterial rings in vitro was investigated at the close of the 10-week study. In norepinephrine-precontracted rings, the relaxations to acetylcholine (ACh) and ADP, as well as to nitroprusside, 3-morpholinosydnonimine, and isoproterenol were attenuated in hypertensive rats on 1.1% calcium supplementation. In the presence of NG-nitro-L-arginine methyl ester (L-NAME), the relaxations to ACh in hypertensive animals on normal calcium were practically absent, whereas in normotensive rats and calcium-supplemented hypertensive rats, distinct relaxations to higher concentrations of ACh were still present. These responses were reduced by 30% to 50% with apamin, a blocker of Ca2+-activated K+ channels, and were further inhibited by blockade of ATP-dependent K+ channels with glyburide. Interestingly, relaxations elicited by ACh and ADP during precontraction with 60 mmol/L KCl (preventing endothelium-dependent hyperpolarization) were not impaired in hypertensive animals. The contractile sensitivity of endothelium-intact arterial rings to 5-hydroxytryptamine and norepinephrine was higher in hypertensive rats on either normal or high-calcium diet, whereas the increase in contractile sensitivity caused by L-NAME corresponded in all groups.
  
  
  CONCLUSIONS
  High-calcium diet markedly opposed experimental DOC-NaCl hypertension, an effect associated with improved arterial relaxation, while abnormalities of vascular contractile properties remained unaffected. In particular, the hyperpolarization-related component of endothelium-dependent arterial relaxation, mediated via opening of arterial K+ channels, could be augmented by calcium supplementation in DOC-NaCl hypertension.
authors.affiliation: University of Tampere, Medical School, Department of Pharmacology, Finland.
authors.forename: H
authors.initials: H
authors.lastname: Mäkynen
authors.forename: M
authors.initials: M
authors.lastname: Kähönen
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.forename: P
authors.initials: P
authors.lastname: Arvola
authors.forename: I
authors.initials: I
authors.lastname: Pörsti
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002136:Calcium, Dietary / Q000494:pharmacology* / Q000627:therapeutic use; D003900:Desoxycorticosterone; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology*; D005905:Glyburide / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009543:Nifedipine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D011921:Rats, Inbred WKY; D012701:Serotonin / Q000494:pharmacology; D012965:Sodium Chloride; D014664:Vasodilation / Q000187:drug effects
chemical_list: D002136:Calcium, Dietary; D015221:Potassium Channels; D009599:Nitroprusside; D001030:Apamin; D012701:Serotonin; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D000244:Adenosine Diphosphate; D001120:Arginine; D009543:Nifedipine; D000109:Acetylcholine; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine