Variations d’Activité de la Cortico surrénale et de l’Appareil hypothalamo-hypophysaire chez le Rat maintenu en Hypercapnie de longue Durée

Abstract

Introduction: The function of the adrenal cortex is often modified during chronic respiratory insufficiency. Most results reported concern experiments on animals or men subjected to CO 2 during short periods of time. The clinician, in cases of chronic respiratory insufficiency, is confronted with a very complex situation, involving a great number of factqrs. Clinical and experimental results of different authors seem to indicate that the adrenal deficiency that is often found in these cases is secondary to that of the higher nervous centers. This work was therefore planned in order to study the degree of activity at the different levels of the hypothalamic-pituitary-adrenal axis in the rat after prolonged hypercapnia. Material and Methods: 34 female Wistar rats were studied: 10 animals were killeed after 8 days and 10 after 15 days of hypercapnia; 14 animals, serving as controls, were sacrificed at the same time as the experimental animals. The experimental rats were placed in a normoxic (20—23% O 2) and hypercarboxic (8 ± 1% CO 2) atmosphere of controlled humidity. At sacrifice the animals were put to sleep with Nembutal. Blood was drawn from the adrenal vein for determination of the corticosteroids and from the abdominal vein for measure of the pH and of the blood gases. After decapitation, the brain with the hypophysis as well as the adrenal glands were dissected. Study of the adrenals comprised various histological, volumetric, karyometric and enzyme methods. For detection of the 3 β hydroxysteroid dehydrogenase activity, the method of Wattenberg was used. Mattingly's method was used for the fluorometric assay of cortisol. Work on the hypothalamus and on the hypophysis comprised histological, volumetric and karyometric studies. Results: The hypercapnic animals present a significant acidosis and a marked hyper-capnemia. The adrenals show: — a significant decrease of the nuclear diameter of the zona glomerulosa cells after 8 days of hypercapnia; — an important accumulation of lipids in the zona fasciculata; — an increased 3 β hydroxysteroid dehydrogenase activity during the entire experimental period; — a statistically significant decrease in plasma cortisol after 15 days of hypercapnia. The hypothalamic-pituitary complex shows: — an involution of the pars intermedia of the hypophysis after 2 weeks of hypercapnia; — hyperplasia of ACTH cells; — a smaller nuclear diameter of the supraoptic cells after 2 weeks of hypercapnia (8.88 ± 0.22 μ against 9.24 ± 0.29 μ for the controls). Discussion: As the 3 μ hydroxysteroid dehydrogenase activity is increased, production of corticosteroids must be enhanced in hypercapnic rats. Sudanophilic lipids accumulate in the zona fasciculata cells, while the level of plasma cortisol is lowered: this seems to point to an evident dysfunction between the secretory and excretory activities of the adrenal cells. The decreased activity of the zona glomerulosa can not be explained because in preceeding tests no variations of the natremia could be found. It may be interesting to note that in a preceeding work on S.P.F. female rats no important differences could be observed between normal and hypercapnic animals.