Effects of high calcium diet on arterial smooth muscle function and electrolyte balance in mineralocorticoid-salt hypertensive rats

P Arvola, H Ruskoaho, I Pörsti

Research output: Contribution to journalArticleScientificpeer-review

28 Citations (Scopus)

Abstract

1. The effects of a high calcium diet (2.5%) on blood pressure, electrolyte balance, plasma and tissue atrial natriuretic peptide (ANP), cytosolic free Ca2+ concentration ([Ca2+]i), and arterial smooth muscle responses were studied in one-kidney deoxycorticosterone (DOC)-NaCl hypertensive Wistar rats. 2. Calcium supplementation for 8 weeks markedly attenuated the development of DOC-NaCl hypertension and the associated cardiac hypertrophy, and prevented the DOC-NaCl-induced sodium-volume retention as judged by reduced plasma Na+, and decreased plasma and ventricular ANP concentrations in high calcium-fed DOC-NaCl rats. However, calcium supplementation did not affect the DOC-NaCl-induced rise in platelet [Ca2+]i. 3. Smooth muscle contractions of isolated mesenteric arterial rings in response to depolarization by K+ (20-30 mM) were enhanced in DOC-NaCl-treated rats, this enhancement being abolished by concurrent oral calcium loading. The Ca2+ entry blocker nifedipine (10 nM) inhibited the contractions induced by K+ (30-125 mM) more effectively in DOC-NaCl rats than in controls, while the inhibition in calcium-loaded DOC-NaCl rats was significantly greater than in controls only with 30 mM K+. 4. The contractions of mesenteric arterial rings induced by omission of K+ from the organ baths were used to evaluate cell membrane permeability to ions. In chemically denervated rings the onset of the gradual rise in contractile force in K(+)-free medium occurred earlier, and the rate of the contraction was faster in DOC-NaCl-treated rats than in controls and high calcium-fed DOC-NaCl rats. Smooth muscle relaxation induced by 0.5 mM K+ upon K(+)-free contractions was clearly slower in DOC-NaCl rats than in controls and calcium-supplemented DOC-NaCl rats. 5. The functions of arterial smooth muscle Na+, Ca2+ exchange and Ca(2+)-ATPase were evaluated by the aortic contractions elicited by low Na+ medium, and the subsequent relaxation responses induced by Ca(2+)-free solution (in the presence of 5 mM caffeine, 1 microM nifedipine and 10 microM phentolamine). The rate of aortic low Na+ contractions (evaluating Ca2+ influx via Na+, Ca2+ exchange), as well as that of subsequent relaxations was slower in DOC-NaCl-treated rats than in controls, whether the relaxation was induced in normal (144.0 mM) or low (1.2 mM) organ bath Na+ concentration (reflecting Ca2+ extrusion by both Ca(2+)-ATPase and Na+, Ca2+ exchange, and by Ca(2+)-ATPase alone, respectively). However, in calcium-supplemented DOC-NaCl rats the aortic responses did not differ from control. The difference between the relaxation rate in normal and low Na+ concentration in each aortic ring,representing the contribution of Na+, Ca2+ exchange in these relaxations, was comparable in all groups.6. In conclusion, calcium supplementation clearly attenuated the development of hypertension, cardiac hypertrophy, and sodium retention induced by the DOC-NaCI treatment. However, the associated rise in platelet [Ca2+], was not prevented, suggesting that in this form of experimental hypertension increased dietary calcium does not lower blood pressure by reducing [Ca2+]i. The results from vascular responses in vitro suggest that in arterial smooth muscle the DOC-NaCl treatment increased contractile sensitivity to depolarization, voltage-dependent Ca2+ entry and cell membrane permeability to ions, and attenuated relaxation responses and vascular Na+, K+-ATPase function. The results further suggest reduced ability of the cell membrane to transport Ca2+ (possibly via Ca2+-ATPase) in DOC-NaCl hypertension. The high calcium diet opposed these alterations. The present results thus provide evidence that the antihypertensive effect of a high calcium diet in mineralocorticoid-salt hypertension is mediated by its beneficial effects on systemic sodium balance and arterial smooth muscle function.

Original languageEnglish
Pages (from-to)948-958
Number of pages11
JournalBr J Pharmacol
Volume108
Issue number4
DOIs
Publication statusPublished - Apr 1993
Externally publishedYes
Publication typeA1 Journal article-refereed

Keywords

  • Animals
  • Aorta, Thoracic/drug effects
  • Atrial Natriuretic Factor/blood
  • Blood Platelets/metabolism
  • Blood Pressure/drug effects
  • Body Weight/drug effects
  • Calcium, Dietary/pharmacology
  • Cell Membrane/drug effects
  • Cell Membrane Permeability/drug effects
  • Desoxycorticosterone
  • Heart/drug effects
  • Hypertension/chemically induced
  • In Vitro Techniques
  • Male
  • Mesenteric Arteries/drug effects
  • Muscle Contraction/drug effects
  • Muscle, Smooth, Vascular/drug effects
  • Organ Size/drug effects
  • Rats
  • Rats, Wistar
  • Water-Electrolyte Balance/drug effects

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