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The effect of calcitriol on atrial natriuretic factor release from isolated atrium
1Department of Medicine, University Hospital, University of British Columbia, Vancouver, Canada.
Insights
Calcitriol, a vitamin D hormone, lowers atrial natriuretic factor (ANF) release from the heart. This effect is independent of changes in blood calcium levels, suggesting a direct hormonal interaction.
Area of Science:
- Endocrinology
- Nephrology
- Cardiology
Background:
- Idiopathic hypercalciuria (IH) patients exhibit low plasma atrial natriuretic factor (ANF) and high calcitriol levels.
- Previous research in our lab established a correlation between depressed ANF and elevated calcitriol in IH patients.
Purpose of the Study:
- To investigate the direct impact of calcitriol on ANF release from isolated atria.
- To elucidate the mechanism by which calcitriol influences ANF secretion, specifically examining its dependence on plasma calcium levels.
Main Methods:
- Isolated atria were perfused with varying concentrations of calcitriol (1-10 ng) to measure ANF release.
- Perfusate calcium levels were acutely altered to assess their effect on ANF secretion.
- ANF release was quantified under different calcitriol and calcium conditions.
Main Results:
- Calcitriol administration led to a dose-dependent reduction in ANF release, with maximal suppression observed beyond 10 ng.
- Acute increases in perfusate calcium elevated ANF release, while reductions decreased it.
- Calcitriol's suppression of ANF release occurred independently of changes in perfusate calcium concentrations.
Conclusions:
- Acute calcitriol administration significantly decreases ANF release from isolated atria.
- The observed reduction in ANF release by calcitriol is mediated through a mechanism independent of alterations in plasma calcium.
- These findings suggest a direct regulatory role of calcitriol on cardiac ANF secretion, potentially contributing to the pathophysiology of idiopathic hypercalciuria.
Abstract:
Previous studies in our laboratory have shown that patients with idiopathic hypercalciuria (IH) have low basal atrial natriuretic factor (ANF) levels in the plasma. These depressed ANF levels are associated with a high plasma calcitriol levels. In this study, we have evaluated the effect of acute calcitriol administration on ANF release in the isolated atrium. There was a gradual reduction of ANF release as the dosage of calcitriol increased from 1 ng to 10 ng. Beyond 10 ng, additional suppression of ANF release by calcitriol was not observed. These results indicate that acute calcitriol administration causes a significant decrease in ANF release. To further determine whether this reduction in ANF release is due to changes in plasma calcium, additional studies were conducted to examine the effect of acute changes in perfusate calcium on ANF release by isolated atria. Acute elevation of perfusate calcium caused an increase in ANF release, whereas a reduction significantly decreased the secretory rate. These observations suggest that calcitriol affects ANF release by a mechanism not dependent on changes in plasma calcium.