Alloxan-induced diabetes in young vs old Sprague-Dawley rats.
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Aging↗
Biomedical subjects
B C Wexler
Publications and source records attributed to B C Wexler.
Histopathologic changes in aging male vs female spontaneously hypertensive rats.
Spontaneously hypertensive rats (SHR) were autopsied at timed intervals from weaning to 28 months. Blood pressure reached 180 to 240 mm Hg after 4 months and was maintained. After 20 months, male SHR began to die of myocardial infarction. A survey was made of the histopathologic changes associated with increasing blood pressure and age. Histopathologic changes appeared in males when they became 8 months old; degenerative changes did not appear in female SHR until 12 to 15 months. Degenerative changes consisted of pituitary basophilia, fatty liver, islet hyperplasia and beta cell degranulation which preceded and became exacerbated with worsening hypertension. Intimal fibrino hyalin lesions of the gonads, polyarteritis nodosa, myocardial infarction, and cerebral edema were more severe in males vs females. Female SHR live significantly longer than males (e.g., 28 to 34 months). Hypertension and longevity may be under separate genetic control in SHR.
Aging↗
Inhibition of the pathogenesis of spontaneous hypertension in spontaneously hypertensive rats by feeding a high fat diet.
Spontaneously hypertensive (Okamoto-Aoki) rats (SHR) and normotensive (Wistar-Kyoto) rats (WKY) were fed a regular or a high fat diet when they were weaned; animals from each group were autopsied at 60, 90, 230, 250, and 180 days of age. SHR fed the high fat diet were cachectic, their pituitary glands were abnormally small, and despite severe hyperlipidemia, hyperglycemia, and adequate corticosterone levels, their zona glomerulosae were completely depleted of lipid, and they did not develop hypertension (110-115 mm Hg) or any manifestation of atheromatous changes. WKY fed the high fat diet became obese, their pituitary glands increased in size, and their normal blood pressure was slightly reduced (90-115 mm Hg). SHR fed the regular diet developed their usual severely elevated hypertension (185-205 mm Hg). It is suggested that the introduction of a high fat diet at an early age will cause hypopituitarism and inhibit the spontaneously appearing hypertension in SHR.
Aging↗
Hypersensitivity of spontaneously hypertensive rats (SHR) to heat, ether, and immobilization.
The responses to immobilization, ether, and heat of spontaneously hypertensive rats (SHR) and normotensive Sprague-Dawley rats (S-D) were compared. Hyperglycemia reached a maximum within 5 min of exposure and was most intense in SHR. There were no differences in the pituitary content of GH or PRL between the SHR and S-D. Circulating GH levels were especially depleted in SHR 15 min post exposure, with rebound to high blood levels at 1 h. Circulating PRL levels were slightly higher in quiescent SHR vs. S-D but surged to much higher levels post exposure in SHR vs. S-D. Postexposure blood corticosterone and aldosterone levels rose to much higher levels in SHR vs. S-D. Although the blood glucose, GH, PRL, corticosterone, and aldosterone levels are similar in hypertensive SHR and normotensive S-D under quiescent conditions, SHR appear to be much more sensitive and respond more vigorously to heat, ether, and immobilization. It is suggested that abnormal activity of the hypothalamic-pituitary system may play a role in the pathogenesis of the genetically programmed hypertension of SHR.
Aldosterone↗
Circadian rhythm of circulating aldosterone in spontaneously hypertensive rats.
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Aldosterone↗
Hyperprolactinemia and hyperadrenocorticism accompanied by normal blood pressure in Sprague-Dawley rats.
Pituitary glands removed from adult female normotensive Sprague-Dawley (S-D) rats were implanted beneath the renal capsule of 100-day male S-D rats. Female neonatal S-D rats were given a single sc injection of 1.25 mg of testosterone proprionate (TP) suspended in sesame oil. Systolic blood pressure and blood samples were taken at various time intervals postimplantation and TP treatment prio to autopsy. Both the TP treatment and pituitary implants caused hyperprolactinemia, increased adrenal weight concomitant with thymus gland involution, hypersecretion of corticosterone, but no increase in systolic blood pressure. It is suggested that the failure of these hyperprolactinemic S-D rats to develop hypertension was due to the absence of a genetically mediated hypertensinogenic factor present in this normotensive strain which is activated by chronic hyperprolactinemia.
Adrenal Glands↗
Ameliorative effects of adrenalectomy on the hyperphagia, hyperlipidaemia, hyperglycaemia and hypertension of obese, spontaneously hypertensive rats (Obese/SHR).
Genetically obese and hypertensive rats (Obese/SHR) were subjected to sham or bilateral adrenalectomy at 4-5 weeks of age with the onset of hyperphagia. The sham-operated Obese/SHR ate voraciously and by 180 days of age males weighed 700 g and females 590 g. The adrenalectomized Obese/SHR ate much less and weighed 325 and 225 g. The systolic blood pressure of the intact Obese/SHR ranged from 160 to 170 mmHg, whereas the blood pressure of the adrenalectomized animals ranged from 108 to 110 mmHg. The thymi of the intact Obese/SHR were massive compared to those of the adrenalectomized rats. Adrenalectomy effectively reduced the hyperinsulinaemia, adiposity, hyperlipidaemia, hyperglycaemia, and elevated BUN levels of the obese rats. Several obese rats had old or new myocardial infarcts, fatty livers, giant-sized islets of Langerhans, nodular and hyperaemic adrenal glands, narrow zona glomerulosa devoid of lipid, vacuolated inner cortical zones, foci of intimal fibrinohyalin deposits in mesenteric arteries, early glomerulosclerosis, and large, rounded bladder calculi. The adrenalectomized Obese/SHR displayed none of these stigmata. It is suggested that the genetically programmed obesity and hypertension in these SHR are mediated by abnormal activity of the hypothalamic-pituitary-adrenal-gonadal axis, may be likened to Cushing's disease in the human, and is associated with accelerated ageing.
Adrenalectomy↗
Kidney and bladder calculi in spontaneously hypertensive rats.
Naturally occurring kidney stones are rare in animals. The Japanese strains of spontaneously hypertensive rats (SHR) are normotensive at birth but develop high blood pressure, hyperglycaemia and hyperlipidaemia as they mature. The SHR strain is prone to develop kidney stones. A unique sub-strain of SHR has been developed in which some animals develop hypothalamic obesity concomitantly with their rising blood pressure, i.e. Obese/SHR. The Obese/SHR characteristically develop microscopic kidney stones which become detached at an early stage of formation, migrate to the bladder, and grow by concretion into huge, rounded calculi. The stone nidus starts as a subepithelial cyst-like focus containing oedema, colloidal acidic mucoprotein, and red and white blood cells suspended on a delicate network of fibrils. THe nidi grow by concretion of an admixture of calcium and acidic protein in a lamellar arrangement. The disparate morphogenesis and anatomic location of kidney stones in Obese is opposed to non-obese/SHR suggest that calculus formation may be governed by specific differences in genetic programming. The incidence of kidney stones parallels the severity and chronicity of the hypertension in SHR, non-obese and Obese/SHR, and the Cushingoid habitus in the Obese/SHR.
Animals↗
Histochemical demonstration of increased adrenomedullary catecholamine secretion in repeatedly bred arteriosclerotic rats.
Male and female, Sprague-Dawley rats were subjected to repeated breeding. When the female breeders had completed 4 closely-spaced pregnancies and had suckled 5 to 10 young after each pregnancy, the breeder rats were killed along with male and female virgin rats of the same age (controls). Male breeders developed microscopic aortic sclerosis (21/24), female breeders manifested grossly visible aortic sclerosis (18/24) ranging from minimal to severe degree, and the remaining females (6/24) had microscopic aortic sclerosis. Virgin rats were free of arterial disease. The arterial lesions consisted of copious subintimal and medial mucopolysaccharide pooling, subintimal fibrosis, elastolytic and intense calcific and cartilaginous alterations. The adrenal medullae of the arteriosclerotic breeder rats reacted positively to AgNO3-glutaraldehyde which demonstrates the presence of catecholamines, e.g., noradrenaline and adrenaline. The intensity of the histochemical reaction parallel the severity of aortic sclerosis. The medullary cells of female breeders were hyperplastic and pleomorphic. Pheochromocytomas were found in female breeders with the most advanced aortic sclerosis. It is suggested tht overactivity of the adrenal cortico-medullary axis contributes to the pathogenesis and morphologic characteristics of the arteriosclerosis, accelerated aging, and the Cushing's disease-like spectrum of degenerative changes which develop spontaneously in repeatedly-bred rats.
Adrenal Medulla↗
Appearance of grossly-visible aortic sclerosis in breeder rats: reconfirmation and up-date, 1957-1981.
Multiparous Sprague-Dawley rats were killed at 7, 14, and 21 days of gestation, at parturition, after 7, 14 and 21 days of lactation, and at 7 and 14 days post-weaning of their fourth reproductive cycle. Grossly visible aortic sclerosis appeared and became progressively more severe during gestation, parturition, and early lactation. Although some of the female breeders had no detectable, grossly-visible aortic sclerosis, all of the 4-time breeders had microscopic aortic sclerosis. Progressive deterioration of the aortic elastic tissue and ground substance was particularly prevalent during the gestation and lactation phases. Calcification and cartilaginous metaplasia appeared during the post-weaning phase. Virgin control rats, equal in age to the 4-time breeders, were completely free of arterial disease. It is believed that abnormal activity of the hypothalamic-pituitary-adrenal axis in association with repeated breeding conditions these animals toward premature arteriosclerosis.
Aging↗
Circadian rhythm of circulating corticosterone and prolactin levels in spontaneously hypertensive rats.
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Animals↗
Good versus moderate regulation of alloxan-induced diabetes in arteriosclerotic and nonarteriosclerotic rats.
Nonarteriosclerotic (virgin) and arteriosclerotic (breeder) rats were made diabetic with alloxan. Animals were treated with constantly adjusted doses of insulin, occasionally adjusted doses, or no treatment. The obese breeder rats lost weight; the lean virgin rats gained weight. All of the animals were autopsied 5 months post-alloxan. Blood pressure increased in virgin rats; the pre-existent mildly elevated blood pressure of arteriosclerotic breeder rats decreased. Glucosuria was effectively reduced in animals accorded good control; blood glucose was not effectively controlled. Circulating nonesterified fatty acids and triglycerides were more effectively normalised by insulin therapy. The diabetes was accompanied by adrenal hypertrophy, thymus gland involution, and increased circulating corticosterone. Virgin rats (68%) developed arterial disease when made alloxan-diabetic; treatment with insulin completely prevented arterial disease. Breeder rats with pre-existent arteriosclerosis showing worsening of their cardiovascular disease; when made severely diabetic those provided with good control of their diabetes were protected against exacerbation of their vascular disease.
Animals↗
Susceptibility and resistance of Sprague--Dawley and spontaneously hypertensive rats to aortic calcification induced by a diet high in CaPO4.
Male and female, Sprague--Dawley (S--D) and spontaneously hypertensive rats (SHR) with arteriosclerosis (breeders) and without arteriosclerosis (virgins) were fed a regular control diet or a diet high in CaPO4. After 45 days on the high Ca : P diet, there were no obvious adverse effects on the health, body, or organ weights of any animals. Although the high Ca : P diet did not cause any exacerbation of the spontaneous high blood pressure of SHR, it did cause hyperlipidemia and abnormally elevated corticosterone levels, but paradoxically, low normal levels of circulating Ca and P. Despite the fact that the high Ca : P diet produces kidney stones, there was no increase in the incidence of kidney stones which appear spontaneously in breeder rats. The high Ca : P diet did not alter the intimal hyalin lesions of the gonadal arterioles which appear spontaneously and exclusively in SHR breeders but it did produce severe exacarbation of the aortic calcification which appears spontaneously in repeatedly bred, S--D rats.
Animals↗
Pathophysiologic responses of spontaneously hypertensive rats to arterial magnesium--aluminum wire implants.
Magnesium--aluminum (Mg--Al) alloy wire was surgically implanted in the abdominal aorta and carotid and renal arteries of virgin (no arterial disease) and breeder (testicular and ovarian arterial lesions) spontaneously hypertensive rats (SHR). The Mg--Al implants promptly dissolved causing increased adrenal glandular weight, thymic involution, depression of the abnormally elevated blood pressure, and poor growth. Serum enzymes (CPK, SGOT, SGPT and LDH) were elevated, circulating levels of triglycerides and cholesterol were reduced, corticosterone and deoxycorticosterone secretion increased. Histologically, fibrocellular, intimal lesions, rich in ground substance, developed about the Mg-Al implants. Occlusive thromboses with cholesterol-positive clefts appeared in the Mg-Al-implanted carotid arteries of breeder SHR with preexisting arterial (limited to gonadal arterioles) disease. It is suggested that adrenocortical and gonadal hormonal factors may condition the responsiveness of the arterial wall of SHR to injury and repair.
Aluminum↗
Estrogen and testosterone sensitivity of middle-aged female rats in the regulation of LH.
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Aging↗
Induction of diverse arterial and myocardial lesions by adrenal regeneration hypertension in Sprague-Dawley versus spontaneously hypertensive rats.
Nonarteriosclerotic, virgin, Sprague-Dawley (SD), and spontaneously hypertensive (SHR) rats and arterio sclerotic breeder SD and SHR rats were subjected to adrenal regeneration-induced hypertension (ARH) with and without extra salt. ARH caused a marked increase in the blood pressure of SD rats and a mild increase in SHR rats; extra salt caused exacerbation of hypertension in SD rats only. Heart and kidney weights were greatly increased commensurate with blood pressure. Increased adrenal weight concomitant with thymus gland involution was considerable in SD and less marked in SHR rats. Testes and ovaries were involuted. Creatine phosphokinase and lactic dehydrogenase levels were abnormally high; blood triglycerides, FFA, glucose, and corticosterone decreased, and total cholesterol, glucose, and corticosterone increased in SD but decreased in SHR rats. Blood urea nitrogen levels were much more abnormally elevated in SD than in SHR rats. ARH did not induce arterial disease in the virgin SD or SHR rats, but it did produce a spectrum of arterial disease in SH breeders, e.g. aortic sclerosis, polyarteritis nodosa-like lesions, intimal cartilaginous metaplasia, and hyalin fibrosis. Altered adrenocortical steroidogenesis may have conditioned the arterial wall of SHR rats to develop diverse morphological changes, and extra salt is much more detrimental to normotensive rats (SD) than to genetically hypertensive rats.
Adrenal Glands↗
Changes in the morphology and location of arterial lesions in virgin and breeder Sprague-Dawley and spontaneously hypertensive rats (SHR) to adrenal regeneration hypertension.
Repeatedly bred, spontaneously hypertensive rats (SHR), unlike breeder Sprague-Dawley (S-D) rats, develop intimal hyalin lesions of the small sized gonadal arteries exclusively. When subjected to adrenal regeneration hypertension (ARH), breeder SHR develop aortic sclerosis identical to the arteriosclerosis which appears in breeder S-D rats. virgin and breeder S-D and SHR were subjected to ARH and were killed 8 weeks later. ARH caused a much greater increase in the blood pressure of S-D than in SH rats. Circulating levels of aldosterone, deoxycorticosterone, and corticosterone were significantly lower in the ARH-treated S-D and SH rats. The regenerated adrenal cortices of the S-D rats manifested extensive lipid depletion indicative of active synthesis and discharge; the regenerated cortices of SHR were replete with lipid suggestive of depressed steroidogenesis. The diverse morphology and anatomical location of arterial lesions in virgin vs breeder SR may be related to adrenal steroidogenesis.
Adrenal Glands↗
Pathophysiological differences between obese and non-obese spontaneously hypertensive rats.
A genetic variant of the spontaneously hypertensive rat (SHR) has been produced which becomes markedly obese as well as hypertensive, i.e. Obese/SHR weigh 800 g as against 300 g for non-obese cohorts. Serum enzymes (CPK, SGOT, SGPT and LDH) are frequently abnormally elevated, concomitantly with a high incidence of myocardial necrosis. Obese/SHR are hyperlipidaemic with severe fatty infiltration of the liver; they are hyperglycaemic with enormous islets of Langerhans and extensive beta-cell degranulation; despite elevated blood urea nitrogen (BUN) levels, they manifest little or no renal damage. Measurement of corticosterone, deoxycorticosterone (DOC) and aldosterone in Obese/SHR demonstrate marked hyper-responsiveness to moderate stress. Circulating prolactin levels are lower in Obese and non-obese/SHR compared to SHR, but Obese/SHR manifest unusually high increases incirculating prolactin levels in response to stress. Obese/SHR are hyperinsulinaemic and have subnormal growth-hormone levels. Desite mild hypertension, hyperglycaemia and hyperlipidaemia, Obese/SHR show no evidence of atheromatous change but do develop early polyarteritis nodosa. It is believed that the genetically programmed hypertension and hyperglycaemia is mediated by increased DOC, aldosterone and corticosterone production respectively, and that the obesity, hypertension, and diabetes in Obese/SHR may be likened to human Cushing's disease.
Aging↗