Regulation of sodium, calcium and vitamin D metabolism in Dahl rats on a high-salt/low-potassium diet: genetic and neural influences.
1. A dietary combination of high salt and low potassium (HSLK) exacerbates hypertension in Dahl salt-sensitive (DS) rats and renders previously normotensive Dahl salt-resistant (DR) rats hypertensive. In both strains, the severity of hypertension correlates with urinary calcium loss. However, the magnitude of excretory calcium losses is significantly greater in DS rats and is potentiated by chemical sympathectomy in both strains. 2. We hypothesized that a defect in vitamin D metabolism may underlie the observed strain-dependent differences in calcium balance. 3. Arterial blood pressure (ABP), water and mineral balance and serum concentrations of 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3) and 25-hydroxyvitamin D3 (25(OH)D3) were measured in intact and chemically sympathectomized (6-hydroxydopamine; 6-OHDA) DS and DR rats after 8 weeks on a HSLK diet. 4. Chronic ingestion of this diet resulted in marked and moderate levels of hypertension in DS and DR rats, respectively. The hypertension was abated and eliminated by 6-OHDA in the DS and DR strains, respectively. Independent of treatment, DS rats had significantly higher urinary excretion of calcium and reduced intestinal absorption of the ion compared with DR rats. The DS rats had significantly higher serum levels of 1,25(OH)2 D3 and markedly lower serum levels of 25(OH)D3 than DR rats. Chemical sympathectomy tended to increase 1,25(OH)2 D3 and to decrease 25(OH)D3 levels in both strains. 5. These data indicate a genetic difference in vitamin D metabolism between DS and DR rats. The abnormally elevated levels of 1,25(OH)2 D3 in DS rats may be an appropriate compensatory response to excessive excretory calcium loss and reduced target organ sensitivity to the hormone and may, maladaptively, directly contribute to hypertension, by stimulating vascular smooth muscle contractility.
Wu
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Department of Physiology, University of Toronto, Mount Sinai Hospital, Ontario, Canada.
Vieth
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Milojevic
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Sonnenberg
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Melo
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LG
D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002112:Calcifediol / Q000097:blood*; D002117:Calcitriol / Q000097:blood*; D002118:Calcium / Q000652:urine*; D008297:Male; D009638:Norepinephrine / Q000652:urine; D016627:Oxidopamine / Q000494:pharmacology; D017419:Potassium, Dietary / Q000008:administration & dosage; D051381:Rats; D020303:Rats, Inbred Dahl; D012982:Sodium, Dietary / Q000008:administration & dosage / Q000652:urine*
D018663:Adrenergic Agents; D017419:Potassium, Dietary; D012982:Sodium, Dietary; D016627:Oxidopamine; D002117:Calcitriol; D002112:Calcifediol; D002118:Calcium; D009638:Norepinephrine