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Adrenal regeneration hypertension (ARH) was induced in virgin and breeder, spontaneously hypertensive (SHR) and Sprague-Dawley (SD) rats. The blood pressure of the previously normotensive, virgin, SD rats and the SD breeder rats with preexistent mild hypertension became greatly elevated. ARH caused an increase in the preexistent severe hypertension in SHR virgin and breeder rats. Serum enzymes, e.g., CPK, SGOT and LDH, were greatly elevated concomitant with the finding of old and new foci of myocardial necrosis. ARH produced a dichotomous metabolic effect, i.e., elevated cholesterol, glucose, and corticosterone levels in SD rats but reduced levels in SHR rats. The zonae glomerulosae of the regenerated adrenal glands of SD rats were devoid of lipid whereas the zonae glomerulosae of SHR rats were full of lipid. Intact SHR breeder rats develop arterial lesions confined to their reproductive organs but after ARH treatment, they were found to have aortic, coronary and renal arterial lesions which were similar to those which occur, spontaneously, in SD breeder rats. It is suggested that changes in the spectrum of adrenal steroids produced during ARH may contribute to the diverse metabolic changes and the alterations in the usual cardiovascular degenerative changes found in these two strains.

The relation of lactation and weaning to the development of early arterial lesions in the female breeder rat was investigated. Changes in aortic hexosamine and 35S-uptake, which are indicative of ground substance metabolism were correlated with changes in aortic calcium, phosphorus, and 45Ca-uptake during lactation and weaning. Lactation was associated with reduced aortic hexosamine content and lowered uptake of [S]sulfate. Further dynamic changes in aortic metabolism of these substances occurred following weaning in conjunction with an intense calcium uptake in the aorta of some, but not all, of the post-lactation animals. These latter changes were associated with the beginning aortic calcifications. Histopathologically, early arterial lesions developing during lactation, consist of intimal accumulations of mucopolysaccharide capped over by collagen. With repeated breeding cycles, these early lesions become exacerbated with extensive medial calcification occurring in areas rich in mucopolysaccharide and collagen particularly around degenerating elastic fibers. The hormones associated with reproduction and lactation may have a conditioning effect on these arterial connective tissue alterations and the development of arterial degenerative changes.

Adult, male and female virgin and breeder gerbils, fed a low fat diet, were autopsied and a gross and microscopic survey was made of their cardiovascular system as well as of other pertinent organs. Blood from each animal was taken for biochemical analyses. None of the virgin control animals exhibited any abnormalities in either their blood chemistry, vascular system or other organs. The female breeder gerbils displayed minimal to severe grossly-visible arteriosclerosis either within the abdominal aorta or extending throughout the aorta. The majority of male and female breeders had some kind of arterial connective tissue derangement when examined histologically, e.g. , ground substance alterations, elastolytic degeneration or calcification. The serum CPK, triglycerides, free fatty acids, cholesterol, glucose, BUN and cortisol levels were all greatly elevated in the breeder gerbils. It is believed that the spontaneous arteriosclerosis and other metabolic derangements which develop in breeder gerbils is highly reminiscent of a similar "syndrome" found in breeder rats and that the observed hormonal metabolic alterations and attendant vascular degeneration are manifestations of over-activity of the hypothalamic-pituitary-adrenal-gonadal axis in connection with the reproductive effort.