Dexamethasone influences intimal thickening and vascular reactivity in the rabbit collared carotid artery.
Intimal thickening predisposes to atherosclerosis and is often associated with alterations of the vascular reactivity of the artery. We investigated whether dexamethasone inhibited the intimal thickening and reactivity changes induced by a silicone collar placed around the left rabbit carotid artery for 2 weeks. The sham-operated, right artery served as control. Dexamethasone (1 mg/kg/day), given in the drinking water (n = 10) or by a subcutaneous minipump (n = 10), abolished intimal thickening compared to that of both placebo groups (n = 10). Both dexamethasone and the collar suppressed the isometric force development of isolated segments elicited by KCl in organ chamber experiments. The collar raised the sensitivity to serotonin (5-hydroxytryptamine, 5-HT) and the maximum force development (Emax) after normalization for the KCl responses. Dexamethasone exerted complex effects on 5-HT contractions in sham arteries: the curves often became biphasic, and sensitivity and Emax of the first phase were depressed by dexamethasone. In contrast, dexamethasone raised the hypersensitivity of collared arteries to 5-HT even further. Collar and dexamethasone did not influence endothelium-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 the reactivity of the smooth muscle cells in the media appear to be unrelated to the process of intimal thickening.
Van Put
D J
DJ
Division of Pharmacology, University of Antwerp (UIA), Wilrijk, Belgium.
Van Hove
C E
CE
De Meyer
G R
GR
Wuyts
F
F
Herman
A G
AG
Bult
H
H
D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D005938:Glucocorticoids; D003907:Dexamethasone