Treatment of vascular smooth muscle cells with estradiol and beta-adrenergic agonists has an additive effect on cAMP levels, but no additive effect on inhibition of collagen synthesis.
Several studies have suggested that increased cell levels of cAMP result in decreased rates of collagen synthesis. Oestrogen treatment of vascular smooth muscle cells (VSMCs) has been shown to cause increased levels of cAMP and decreased rates of collagen synthesis. Beta-adrenergic agonists are also known to increase cellular levels of cAMP in VSMCs, although the effect of beta-adrenergic agonists on collagen synthetic rates in VSMCs is unknown. Since beta-agonists and oestrogens are commonly used clinical agents these studies were conducted to determine the potential of these agents to have an additive effect on cell cAMP levels and inhibition of collagen synthetic rates. When VSMCs were treated with both oestrogen and isoproterenol there was an additive effect on cellular cAMP levels although the observed decrease in collagen synthetic rates was the same as observed in cells treated with just oestrogen. Treatment of VSMCs with propranolol inhibited isoproterenol-induced changes in cAMP but had no effect on either oestrogen-induced increases in cAMP levels or inhibition of collagen synthesis. The cellular location of cAMP following beta-adrenergic agonist treatment was different from the distribution of cAMP in control or oestrogen-treated VSMCs. This difference in cellular distribution of cAMP may partially explain the absence of collagen synthesis inhibition following beta-adrenergic agonist treatment of VSMCs.
Dimopoulos
George J
GJ
Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, CT, USA.
Langner
Ronald O
RO
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D000242:Cyclic AMP / Q000378:metabolism*; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013726:Terbutaline / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D004958:Estradiol; D003094:Collagen; D011433:Propranolol; D000242:Cyclic AMP; D007545:Isoproterenol; D013726:Terbutaline