Rat natriuretic peptide receptor genes are regulated by glucocorticoids in vitro.
The effects of glucocorticoids on NPR-A and NPR-B mRNA transcription and natriuretic peptides ANP and CNP mediated cGMP production by intact vascular smooth muscle cells (VSMC) were studied in rat. Cultured VSMC were prepared from rat mesenteric arteries of 12-week-old Sprague-Dawley rats by enzymatic digestion. Dexamethasone-induced NPR-A mRNA increase was detectable early in the incubation periods and reached a plateau after 48 hours of glucocorticoid administration. This mRNA increase was mimicked by cortisol and inhibited by the glucocorticoid receptors antagonist RU 38,486. The levels of NPR-B mRNA remained unchanged during all the periods of stimulation. However, cGMP generated by both receptors in dexamethasone treated cells was higher than in control cells and this production was mimicked by cortisol and also blocked by RU 38,486. Desoxycorticosterone acetate (DOCA) had no effect on the levels of cGMP production. The results suggest that glucocorticoids have transcriptional and posttranscriptional effects on rat mesenteric arteries cells through glucocorticoid receptors.
Nuglozeh
E
E
Department of Medicine, St-Luc Hospital, University of Montreal, Quebec, Canada. Nuglozeh@jax.org
Mbikay
M
M
Stewart
D J
DJ
Legault
L
L
D000818:Animals; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017461:Receptors, Atrial Natriuretic Factor / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects; D000099242:Atrial Natriuretic Factor Receptor B
D006152:Cyclic GMP; D003907:Dexamethasone; D005938:Glucocorticoids; D006162:Guanylate Cyclase; D012333:RNA, Messenger; D017461:Receptors, Atrial Natriuretic Factor; D000099242:Atrial Natriuretic Factor Receptor B; C091715:atrial natriuretic factor receptor A