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.