Inhibition of phosphodiesterase has an additive effect on estrogen's ability to inhibit collagen synthesis in vascular smooth muscle cells.
Several studies have shown that estrogen has the ability to decrease collagen synthetic rates in vascular smooth muscle cells (VSMCs) by increasing cellular cyclic AMP (cAMP) levels. Phosphodiesterase inhibitors have also been shown to inhibit collagen synthesis in VSMCs presumably by preventing the degradation of cAMP. Since estrogens and phosphodiesterase inhibitors are used clinically, it is important to determine the potential for phosphodiesterase inhibitors to potentiate estrogen's ability to inhibit collagen synthesis in VSMCs. The results of the present study demonstrate that the phosphodiesterase inhibitors cilostamide and Ro-20-1724 had an additive effect on estrogen's ability to inhibit collagen synthesis in VSMC. Also, the data suggests that phosphodiesterase inhibitors mediated this additive effect by increasing cellular levels of cAMP.
Dimopoulos
George J
GJ
Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, CT, United States. Dimopoulos@BBRI.org
Langner
Ronald O
RO
D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D000242:Cyclic AMP / Q000378:metabolism; D004347:Drug Interactions; D004967:Estrogens / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004967:Estrogens; D010726:Phosphodiesterase Inhibitors; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D003094:Collagen; D000242:Cyclic AMP