Gen. Pharmac. Vol. 31, No. 1, pp. 149–153, 1998 ISSN 0306-3623/98 $19.00 + .00 Copyright  1998 Elsevier Science Inc. PII S0306-3623(97)00387-X Printed in the USA. All rights reserved Effect of Vitamin E on Vascular Responses of Thoracic Aorta in Rat Experimental Arthritis Mehtap G. C ¸ ınar, 1 Cenk Can, 1 Sibel U ¨ lker, 1 S ¸ule Go ¨k, 2 Canan C ¸ oker, 3 Necdet Soykan, 1 Sezen Kos ¸ay 1 and Akgu ¨n Evinc ¸ 1 * 1 Department of Pharmacology and 3 Central Research Laboratory, Faculty of Medicine, Ege University, Bornova, I ˙ zmir, Turkey and 2 Department of Pharmacology, Faculty of Medicine, Celal Bayar University, Manisa, Turkey ABSTRACT. 1. Vascular contractile and relaxant responses were evaluated in isolated aortic rings of adjuvant-induced arthritic rats in comparison with control rats, and the effect of an antioxidant treat- ment on the development of the arthritis was investigated by vitamin E administration (100 mg/kg/day, IM, for 26 days). 2. Arthritis was induced by an intradermal injection of Freund’s complete adjuvant into rat paw. Vascular responses, arthritic lesions and serum copper levels were evaluated after 26 days from adju- vant inoculation. 3. Serum copper levels were significantly lower in arthritic rats than in the control. 4. The contractile response of aortic rings to phenylephrine (PE), but not to KCl, was increased in preparations from arthritic rats, which could be explained by an enhancement of intracellular calcium contents. 5. Acetylcholine (Ach)-mediated endothelium-dependent and sodium nitroprusside (SNP)-medi- ated endothelium-independent relaxations were not changed significantly in vascular preparations from arthritic rats. 6. In arthritic rats, vitamin E treatment improved arthritic lesions with an increase in copper levels. Despite this ameliorating effect, vitamin E treatment caused an increase in contractile response to PE and a decrease in the relaxant response to Ach and SNP in arthritic rats. 7. These data show that vitamin E provides ameliorating effects in improving systemic signs of ex- perimental arthritis, but it fails to restore abnormalities in vascular function, indicating that adjuvant- induced alterations in vascular function may include mechanisms other than oxygen–free radical forma- tion. gen pharmac 31;1:149–153, 1998.  1998 Elsevier Science Inc. KEY WORDS. Adjuvant arthritis, vitamin E, vascular endothelium, vascular smooth muscle INTRODUCTION Indeed, it has been suggested that the aggravation of adjuvant ar- thritis might be associated with lipid peroxidation, and the antioxi- Experimental arthritis induced by a single injection of Freund’s ad- dant properties of vitamin E induced pronounced biochemical ef- juvant (a suspension of heat-killed mycobacteria) has been accepted fects that might be useful in improvement of the disease process as having many histological and clinical features in common with (Kheir-Eldin et al., 1992; Yoshikawa et al., 1983). It has also been human rheumatoid arthritis (Brahn, 1991). This experimental pa- shown that vitamin E supplement protects vascular responses from thology has been suggested to usually be involved in inflammation, impairment associated with atherosclerosis (Stewart-Lee et al., 1994). and a modified reactivity of vascular smooth muscle to several con- In the light of the foregoing, the aim of the present study was to tractile agonists with a diminished endothelium-derived relaxation find out whether adjuvant-induced inflammation may alter the re- has also been observed (Fang et al., 1991; Fontaine et al., 1984). activity of vascular smooth muscle and whether vitamin E treatment These changes in adjuvant arthritis closely resemble those observed may modulate these changes. Furthermore, the serum levels of cop- in hypertension (Gabbiani et al., 1979). per also were determined as an index of inflammation, because an In spite of the numerous studies undertaken to elucidate the etiol- increase in plasma copper levels was accepted as a marker of sys- ogy of the disease, much remains to be done in clarifying the extent temic inflammation (Rofe et al., 1994). and mechanism of the vascular changes observed. Formation of ex- cessive free radicals and lipid peroxidation is one of the topics to fo- cus attention on; the role of oxygen free radicals in human disease MATERIALS AND METHODS processes including arthritis and atherosclerosis has been briefly re- Induction of arthritis viewed (Bulkley, 1983). Lipid peroxidation can be prevented by the Adjuvant arthritis was induced in male adult albino rats (180–200 g) presence of radical scavenging systems, and one of the important by a single intradermal injection of 0.6 mg of heat-killed Mycobacte- members of this system is known to be vitamin E (Machlin, 1991). rium tuberculosis in 0.1 ml mineral oil (Freund’s complete adjuvant, FCA) in the palmar surface of the right hind pad. Paw swelling (measured by using a micrometric compass) and body weights were *To whom correspondence should be addressed. Received 14 January 1997; revised 1 July 1997; accepted 22 August 1997. recorded on days 7, 14, 21 and 26 after injection and compared with