Adenosine inhibits collagen and total protein synthesis in vascular smoothmuscle cells

The objective of this study was to characterize the effects of exogenous, d rug-induced and cAMP-adenosine pathway-derived adenosine on collagen synthe sis by and hypertrophy of vascular smooth muscle cells (SMCs). Confluent va scular SMCs were stimulated with 2.5% fetal calf serum in the presence and absence of adenosine receptor agonists [adenosine, 2-chloroadenosine, N-6-c yclopentyladenosine, 5'-N-ethylcarboxamidoadenosine, 5'-N-methylcarboxamido adenosine, and 2-p-(2-carboxyethyl)phenethylamino-5'-N-adenosine], drugs th at increase levels of endogenous adenosine [erythro-9-(2-hydroxy-3-nonyl) a denine, dipyridamole, and iodotubericidin], and cAMP (increases adenosine b y conversion to AMP and hence to adenosine via the cAMP-adenosine pathway). Adenosine receptor agonists inhibited fetal calf serum-induced collagen an d total protein synthesis las assessed by [H-3]proline and [H-3]leucine inc orporation, respectively) with a relative potency profile consistent with t he effects being mediated by adenosine A(2B) receptors. Erythro-9-(2-hydrox y-3-nonyl) adenine, dipyridamole, iodotubericidin, and cAMP also inhibited collagen and total protein synthesis. The effects of 2-chloroadenosine, ery thro-9-(2-hydroxy-3-nonyl) adenine, iodotubericidin, and cAMP on collagen a nd total protein synthesis were attenuated by KF17837 and 1,3-dipropyl-8-p- sulfophenylxanthine (selective and nonselective A, receptor antagonists, re spectively) but not by 8-cyclopentyl-1,3-dipropylxanthine (selective A(1) r eceptor antagonist). These studies indicate that exogenous, drug-induced an d cAMP-adenosine pathway-derived adenosine inhibit vascular SMC collagen sy nthesis and hypertrophy via A(2B) receptors, Thus, exogenous A(2B) receptor agonists and drugs that modulate endogenous adenosine levels may protect a gainst vasoocclusive disorders by attenuating extracellular matrix synthesi s by and cellular hypertrophy of vascular SMCs. Moreover, the cAMP-adenosin e pathway may protect against vascular hypertrophy.