Glucocorticoids and atrial natriuretic factor receptors on vascular smooth muscle.
The effect of glucocorticoids on the atrial natriuretic factor (ANF)-mediated formation of cyclic guanosine monophosphate (cGMP) by intact vascular smooth muscle cells (VSMC) was studied in rats. Cultured VSMC were obtained from the renal arteries of 14-week-old Wistar rats by the explant method. Micromolar concentrations of dexamethasone, given as pretreatment for 48 hours, suppressed the ANF-mediated response. The dexamethasone-induced suppression was detectable at 6 hours and reached a maximum 24 hours after administration in a dose-dependent manner. Inhibitors of protein synthesis blocked this effect of the glucocorticoid. The basal activity of guanylate cyclase in the dexamethasone-treated cells was lower than in the control cells. Other steroids having glucocorticoid action mimicked this suppression of the ANF-mediated response. This suppression was blocked by a glucocorticoid receptor antagonist. The results suggest that glucocorticoids suppress ANF-mediated cGMP formation by VSMC through glucocorticoid type II receptors and the induction of protein synthesis. Suppression of the ANF-mediated response may play a role in glucocorticoid-induced hypertension.
Yasunari
K
K
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Kohno
M
M
Murakawa
K
K
Yokokawa
K
K
Takeda
T
T
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D006152:Cyclic GMP / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D015735:Mifepristone / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000032:analysis / Q000187:drug effects*
D005938:Glucocorticoids; D011500:Protein Synthesis Inhibitors; D011956:Receptors, Cell Surface; D015735:Mifepristone; D003907:Dexamethasone; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP