Differing patterns of altered glucocorticoid secretion in experimental malignant and benign hypertension. Influences upon the lymphoid system and on arterial connective tissue metabolism.

Abstract

AbstractAlterations in plasma glucocorticoid levels and in the evolution of the thymus gland were studied in groups of malignant (MHY) and benign (BHY) hypertensive rats sacrificed at 6, 9, 12 and 24 days after aortic ligation between the renal arteries. Although the degree of blood pressure elevation was similar in MHY and BHY animals, MHYs were characterised by severe weight loss, increased plasma renin activity and elevated blood urea nitrogen. MHY animals sacrificed at day 6 showed markedly increased plasma corticosterone (PC) levels (PC: 604 ± 3·9 μg/dl) accompanied by severe thymus atrophy (123 ± 19 mg). In 6‐day BHY animals elevated plasma corticosterone and thymus atrophy were also present but were not as marked as in MHY (BHY: PC: 38·8 ± 4·6 μg/dl, thymus wt: 244 ± 33 mg). Values from BHYs were, however, significantly different from sham‐operated (Sham‐op) controls (Sham‐op: PC: 22·6 ± 1·4 μg/dl; thymus wt: 631 ± 32 mg). In BHY animals sacrificed at day 9, plasma corticosterone had returned to baseline levels. From this time period onward, in BHY animals normal plasma corticosterone was accompanied by a steady recovery of the thymus gland, generalised lymphoid proliferation, and by the proliferation of collagen and elastin (measured by the in‐vitro incorporation of 14C‐l‐proline into both proteins) in the intima‐media and adventitia of the thoracic aorta. Contrary to the normalisation of plasma corticosterone and thymus recovery observed in BHYs, corticosterone remained chronically elevated in MHYs and thymus atrophy was present throughout the entire evolution oif the disease. In MHYs, the arterial connective tissue proliferation was repressed and the synthesis of collagen and elastin was similar to normotensive controls. A. Statistically significant decrease in collagen concentration was present in both intima‐media and adventitia of MHYs when compared to either BHMs or normotensive controls. Impaired vascular hypertrophy in MHYs coexisted with marked alterations in the lymphoid system. In the thymus severe atrophy, thymocyte depletion and a reverse corticomedullary pattern were observed. When the thymocytes remaining in the organ were challenged with the T cell mitogen concanavalin A they showed an impaired proliferative response. In the blood a significant reduction in circulating lymphocytes and marked neutrophilia were observed. These findings suggest that increased glucocrticoid secretion marks important modifications in cells and tissues involved in the production of necrotising arterial lesions during the evolution of malignant hypertension.