1,25 (oh)2 vitamin d3 suppresses expression and secretion of atrial
natriuretic peptide from cardiac myocytes.
Wu, J., Garami, M., Cao, L., Li, Q. and Gardner, D. G.
DEPARTMENT OF MEDICINE, AND METABOLIC RESEARCH UNIT, UNIVERSITY OF
CALIFORNIA AT SAN FRANCISCO
APStracts 2:0033E, 1995.
We have examined the effects of 1,25 (OH)2 vitamin D3 on the
expression of the rat atrial natriuretic peptide gene and the
secretion of the encoded protein product in neonatal rat cardiac
myocyte cultures. 1,25 (OH)2 vitamin D3 effected a dose- and time
-dependent inhibition of agonist-stimulated ANP secretion which was
accompanied by a reduction in the levels of the ANP mRNA transcript.
The latter effect appeared to derive, at least in part, from
suppression of ANP gene transcription. Of interest, both the
reduction in mRNA levels and the inhibition of transcriptional
activity were amplified by simultaneous treatment with retinoic acid,
suggesting that heterodimerization of liganded 1,25 (OH)2 vitamin D3
receptor and retinoic acid receptor (likely RXR) may underlie the
inhibitory mechanism in the cardiac myocyte. Neither the secretory
effect nor the effect on transcription proved to be calcium
dependent. 22-oxacalcitriol, a non-hypercalcemic analogue of 1,25
(OH)2 vitamin D3, was equally effective in suppressing ANP mRNA
levels and transcription of the gene. These findings add to a growing
body of data which imply an important role for 1,25 (OH)2 vitamin D3
in the regulation of cardiovascular function.
Received 8 December 1994; accepted in final form 9 February 1995.
APS Manuscript Number E509-4.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 1 March 1995.