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 normot ensive Dahl salt-resistant (DR) rats hypertensive. In both strains, the sev erity of hypertension correlates with urinary calcium loss. However, the ma gnitude 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 o bserved strain-dependent differences in calcium balance. 3. Arterial blood pressure (ABP), water and mineral balance and serum conce ntrations of 1,25-dihydroxyvitamin D-3 (1,25(OH)(2) D-3) and 25-hydroxyvita min D-3 (25(OH)D-3) 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. Independen t of treatment, DS rats had significantly higher urinary excretion of calci um and reduced intestinal absorption of the ion compared with DR rats. The DS rats had significantly higher serum levels of 1,25(OH)(2) D-3 and marked ly lower serum levels of 25(OH)D-3 than DR rats. Chemical sympathectomy ten ded to increase 1,25(OH)(2) DJ and to decrease 25(OH)D-3 levels in both str ains. 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) D-3 in DS ra ts may be an appropriate compensatory response to excessive excretory calci um loss and reduced target organ sensitivity to the hormone and may, malada ptively, directly contribute to hypertension, by stimulating vascular smoot h muscle contractility.