Long-term effect of glucocorticoid on connective tissue of aorta and skin Morphological and biochemical studies of tissues from rabbits with intact and injured aortas

Abstract

The long-term effect of prednisolone, 0.6 mg/day for 63 days, upon mechanically induced inflammation and repair processes in vascular connective tissue was compared with that upon undamaged vascular wall and intact skin of rabbits. The investigations included histological examination of aorta as well as biochemical analyses of collagen and various glycosaminoglycan fractions, RNA, DNA and .alpha.-amino nitrogen. The metabolism of collagen was estimated by in vitro labeling with [14C]proline and the metabolism of glycosaminoglycans by in vivo labeling with [35S]O4. The radioactivity of [125I]albumin in the aorta and serum was also studied. The collagen, glycosaminoglycans, RNA, DNA and water of vascular connective tissue during inflammation and repair and of intact skin was more sensitive to prednisolone action than the connective tissue of undamaged vascular wall. An increased degradation of newly synthesized collagen was observed in damaged aorta as well as in skin in which collagen biosynthesis was also inhibited. Prednisolone inhibited glycosaminoglycan biosynthesis and decreased the total amount of glycosaminoglycans and of nucleic acids in the damaged aortas and the skin. The [125I]albumin aorta-to-serum ratio was significantly increased in the damaged aorta. Prednisolone treatment decreased the ratio in injured aortas, but elevated the ratio in the undamaged vessels. Prednisolone inhibited intimal thickening of the injured aortas. Evidently long-term low dose prednisolone treatment inhibits the late inflammatory and repair processes of the vessel wall with only a minor effect on the undamaged vascular connective tissue. The connective tissue of intact skin is affected more easily than that of the vascular wall. The observations suggest that treatment with glucocorticoids may be of importance also in the control of chronic inflammation of the vascular wall. The sensitivity of the connective tissue of the skin to glucocorticoids may explain some of the side-effects from long-term glucocorticoid treatment.