Glucocorticoid inhibits cAMP production induced by vasoactive agents in aortic smooth muscle cells.
It is well-known that atherosclerotic change and hypertension are common manifestations in patients with glucocorticoid excess. We previously reported that pituitary adenylate cyclase activating polypeptide (PACAP), prostaglandin E2 (PGE2) and carbacyclin, a stable analog of prostacyclin, have suppressive effects on vasopressin-induced DNA synthesis of rat aortic smooth muscle cells through cAMP production (Murase et al., J. Hypertens., 10 (1992) 1505; Oiso et al., Biochem. Cell. Biol., 71 (1993) 156). In the present study, we investigated the effect of glucocorticoid on cAMP production induced by PACAP, PGE2 and carbacyclin in aortic smooth muscle cells. The pretreatment with dexamethasone significantly inhibited cAMP accumulation induced by these vasoactive agents in a dose dependent manner in the range between 10 pM and 10 nM. These inhibitory effects of dexamethasone were dependent on the time of pretreatment up to 8 h. Dexamethasone inhibited cAMP accumulation induced by NaF, a GTP-binding protein activator, and forskolin which directly activates adenylate cyclase. Moreover, forskolin-induced adenylate cyclase activity was significantly reduced in membranes prepared from the cells treated with dexamethasone. These results strongly suggest that glucocorticoid inhibits cAMP production induced by vasoactive agents in primary cultured rat aortic smooth muscle cells and the inhibitory effect is exerted at the level of adenylate cyclase.
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Y
Y
Ito
O
O
Kozawa
H
H
Tokuda
A
A
Suzuki
Y
Y
Watanabe
J
J
Kotoyori
Y
Y
Oiso
D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D011464:Epoprostenol / Q000494:pharmacology; D005938:Glucocorticoids / Q000138:chemical synthesis / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D005938:Glucocorticoids; D011458:Prostaglandins E; D003907:Dexamethasone; D011464:Epoprostenol; D000242:Cyclic AMP