DEXAMETHASONE INFLUENCES INTIMAL THICKENING AND VASCULAR REACTIVITY IN THE RABBIT COLLARED CAROTID-ARTERY

Intimal thickening predisposes to atherosclerosis and is often associa ted with alterations of the vascular reactivity of the artery. We inve stigated whether dexamethasone inhibited the intimal thickening and re activity changes induced by a silicone collar placed around the left r abbit carotid artery for 2 weeks. The sham-operated, right artery serv ed as control. Dexamethasone (1 mg/kg/day), given in the drinking wate r (n = 10) or by a subcutaneous minipump (n = 10), abolished intimal t hickening compared to that of both placebo groups (n = 10). Both dexam ethasone and the collar suppressed the isometric force development of isolated segments elicited by KCI in organ chamber experiments. The co llar raised the sensitivity to serotonin (5-hydroxytryptamine, 5-HT) a nd the maximum force development (E(max)) after normalization for the KCI responses. Dexamethasone exerted complex effects on 5-HT contracti ons in sham arteries: the curves often became biphasic, and sensitivit y and E(max) of the first phase were depressed by dexamethasone. In co ntrast, dexamethasone raised the hypersensitivity of collared arteries to 5-HT even further. Collar and dexamethasone did not influence endo thelium-dependent relaxations elicited by acetylcholine or the calcium ionophore A-23187. It is concluded that dexamethasone interfered with neo-intima formation in the collar model, presumably by inhibition of smooth muscle cell migration and/or proliferation, without restoring contractile behaviour. Therefore, the collar-induced alterations in th e reactivity of the smooth muscle cells in the media appear to be unre lated to the process of intimal thickening.