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Biomedical subjects

B C Wexler

Publications and source records attributed to B C Wexler.

At least 73 records · Page 4Linked to original sources
PubMed1978

Laser beam - induced injury of aortae of arteriosclerotic and nonarteriosclerotic rats.

The abdominal aortae of non-arteriosclerotic (virgin) and arteriosclerotic (breeder) Sprague-Dawley rats were exposed by laparotomy and a microscopically discreet locus within the inner media was subjected to non-thermal injury by a pulsed ruby laser beam (300 joules/cm2). Animals were killed every two days for 8 days. The non-arteriosclerotic rats manifested increased mesenchymal cell activity at the site of injury followed by intimal ground substance accumulation populated by mesenchymal cells and culminating with medial scarring with extensive loss of elastic lamellae. The arterioscelrotic aortae displayed no medial mesenchymal cell reaction but immediately below the lesion site there was active differentiation of intimal mesenchymal cells into cartilaginous cells and eventual transformation of both the intima and media into large C-shaped bars of cartilaginous tissue. It is believed that laser beam injury accelerated the differentiation of the already disturbed mesenchymal cells of the arteriosclerotic animals in the direction of mature cartilage to strengthen a weakened aortic wall.

Animals↗
PubMed1978

Corticotropin stimulation of hypertensive rats with and without arteriosclerosis.

Male and female, nonarteriosclerotic (virgin) and arteriosclerotic (breeder), Sprague-Dawley rats were subjected to the hypertension-producing regimen of uninephrectomy, 1% saline drinking water, and desoxycorticosterone (Percorten) pivalate. Just before autopsy, some of the animals were given a single injection of corticotropin. The acute challenge of corticotropin caused a definite increase in free fatty acids, systolic blood pressure, creatine phosphokinase, glucose, and corticosterone. The two weeks of desoxycorticosterone and 1% saline-induced hypertension caused myocarditis and hyalinization of the coronary arteries of the nonarteriosclerotic (virgin) rats and definite exacerbation of the preexisting arteriosclerosis in breeder rats, severe myocarditis, and polyarteritis nodosa. All of the treated animals manifested lipid depletion of the zona glomerulosa indicative of reduced biosynthesis and secretion of endogenous mineralocorticoids due to the exogenous desoxycorticosterone and saline treatment.

Adrenocorticotropic Hormone↗
PubMed1978

Metyrapone-induced cardiovascular degenerative changes in non-arteriosclerotic and arteriosclerotic rats.

Virgin and breeder, male and female, Sprague-Dawley rats were unilaterally nephrectomized and given 1% saline drinking water. Animals were injected i.p., twice daily, with a 10 mg/100 g body wt dose of the 11-beta hydroxylation inhibitor, Metyrapone. After 7 weeks of treatment, both the previously nonarteriosclerotic virgin rats and the breeder rats with pre-existing arteriosclerosis developed de nove, widely distributed, intimal hyalinization of their peripheral arteries along with myocardial fibrosis and hyalinization of their intramyocardial coronary arteries. The Metyrapone-treated animals developed severe hypertension with greatly elevated serum creatin phosphokinase, glucose, BUN and cholesterol levels. The adrenal glands, hearts, and kidneys were greatly hypertrophied, in keeping with Metyrapone-induced extra ACTH release and the hypertension-induced myocardial and renal histopathology. Uniparous, Metyrapone-treated, female rats manifested an unusually high incidence of saccular aneurysms of the aorta. It is suggested that the hypertension and the intimal hyalinization and other specific morphologic characteristics of the cardiovascular degenerative changes observed were directly related to excess production of mineralocorticoids, e.g., deoxycorticosterone.

Adrenal Glands↗
PubMed1978

Repeated myocardial infarction in non-arteriosclerotic and arteriosclerotic Sprague-Dawley rats.

Adult male Sprague--Dawley rats, with and without arteriosclerosis, were subjected to an isoprenaline-induced myocardial infarction. After 4 weeks' convalescence, the survivors were subjected to a second myocardial infarct. Animals free of arterial disease were able to survive only 2 infarcts, whereas those with preexisting arterial disease were able to endure a third and some a fourth infarct. Changes in serum enzymes (CPK, SGOT, SGPT and LDH), lipids (triglycerides, free fatty acids and cholesterol), glucose, BUN, and corticosterone manifested intensification or diminution of their characteristic response pattern with each subsequent episode of acute myocardial infarction and repair. Many animals died as a result of left ventricular aneurysm formation. Animals with pre-existent coronary artery disease were especially capable of affecting repair of the myocardium or aneurysmal wall through mesenchymal or fibroblastic activity.

Animals↗
PubMed1977

Inhibition of spontaneously developing arteriosclerosis in female breeder rats by adrenalectomy.

In order to determine whether the adrenal glands play a primary or secondary role in the pathogenesis of the spontaneous arteriosclerosis which occurs in repeatedly bred rats, sexually mature female, Sprague-Dawley rats were adrenalectomized and maintained during four successive pregnancies. Some of the breeders were treated with deoxycorticosterone (DOCA) and 0.5% saline. The adrenalectomized breeders did not develop arteriosclerosis, beta cell degranulations, or those which has accesory or regenerated adrenal glandular tissue. Surprisingly, intact DOCA-treated breeders also showed inhibition of arterial disease but they did have fatty livers and beta cell degranulation. Body and organ weights, serum enzymes, lipids, glucose, BUN, and corticosterone were elevated in breeder rats but not to such high levels as is usual in repeatedly bred rats. These findings demonstrate that the presence of the adrenal glands is essential for the pathogenesis of the spontaneous arteriosclerosis, fatty liver, and beta cell degranulation which occurs in repeatedly bred, female rats.

Adrenal Glands↗
PubMed1977

Comparative effects of adrenal regeneration hypertension on non-arteriosclerotic and arteriosclerotic Sprague-Dawley vs spontaneously hypertensive rats.

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 preexisted 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 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.

Adrenal Cortex↗
PubMed1977

Effect of increased serum urate levels on virgin rats with no arteriosclerosis versus breeder rats with preexistent arteriosclerosis.

Healthy virgin and breeder rats (Sprague-Dawley) with naturally occurring hypertension and arteriosclerosis were fed 5% oxonic acid and 1% uric acid added to their regular diet for 30 days. Although rats are able to convert uric acid into excretable allantoin, abnormal urinary and serum urate levels appeared. Males and females, virgins and breeders, differed in the severity of their increased urate levels. Animals with elevated urate levels developed hypertension, hyperglycemia, and hypertriglyceridemia, with only slight changes in cholesterol and free fatty acids. The kidneys were greatly enlarged and manifested medullary streaking indicative of urate deposits but were free of significant damage; BUN levels in these animals were abnormally high. Adrenal glands were reduced in size and depleted of lipid, circulating corticosterone levels were subnormal, and thymi were involuted. Serum enzymes CPK and LDH were greatly increased, whereas SGOT and SGPT levels were not elevated. The abnormal urate levels did not induce de novo arterial disease in the formerly healthy virgin rats and did not cause exacerbation of the pre-existing, naturally occurring arteriosclerosis characteristic of repeatedly bred rats. It is suggested that Sprague-Dawley rats are endowed with an especially efficient hepatic and renal capacity to metabolize uric acid. Increased urate levels in rats may have some direct metabolic relationship to the production of hypertension, hyperglycemia, and hypertriglyceridemia.

Animals↗
PubMed1977

Acute cerebrovascular and myocardial ischemia superimposed upon chronically hypertensive and arteriosclerotic male Sprague-Dawley rats.

Repeatedly bred male rats which develop arteriosclerosis spontaneously were subjected to unilateral nephrectomy, 1% saline drinking water, and 2 mg subcutaneous injections of deoxycorticosterone acetate per animal weekly for 7 weeks to induce severe hypertension (+/- 175 mmHg systolic). Acute cerebral ischemia was induced by ligating one carotid artery. Two days later, experimental animals were subjected to acute myocardial ischemia by injecting them subcutaneously with a single dose of isoproterenol (25 mg/100 g body weight). All of the experimental animals died within 4 hours of the injection of isoproterenol. During this same period, blood pressure, body weight, thymus, kidney, and testicular weights were reduced, whereas heart and adrenal gland weights increased markedly. Serum enzymes (CPK, SGOT, and LDH), lipids (triglycerides and free fatty acids), glucose, BUN, and corticosterone rose progressively. Fatty infiltration of the liver, adrenal hyperplasia, myocardial thrombi, renal degenerative changes, and cerebral edema became progressively more severe. A hypothalamic-pituitary-adrenal axis component may be involved in the reaction to the stress of acute cerebral or myocardial ischemia, which is intensified when the two ischemias are combined, and chronic hypertension may exacerbate both.

Animals↗
PubMed1977

Alloxan diabetes in spontaneously hypertensive rats: gravimetric, metabolic and histopathological alterations.

In order to investigate the combined effects of diabetes and hypertension on the pathogenesis of cardiovascular disease, adult male and female SHR rats which develop hypertension spontaneously were given a single, 10 mg or 15 mg/100 g body wt. injection of alloxan s.c. to induce moderate or severe diabetes. Insulin was deliberately withheld. Animals were examined by autopsy daily for 7 days post-alloxan and after 4 and 8 weeks. Mortality was high--only 52% of the males survived as against 80% of the females. Most deaths occurred on Day 5 and were associated with adrenal haemorrhage and hyperplasia, thymus galnd involution, fatty liver and marked hypotension despite elevated aldosterone levels. During the first week, corticosterone levels increased significantly in the male; in females they showed little change. After 4 weeks, the severly diabetic animals became emaciated and moribund; corticosterone and aldosterone levels fell to very low levels despite adrenal hyperplasia. The beta cells of the moderately diabetic animals eventually lost their ability to secrete insulin and these animals too became cachetic and moribund with concomitant elevation of lipid, glucose and BUN levels, as well as myocardial infarction, fatty liver, and generalized hyalin arteriolo-, arterio-, and nephrosclerosis. It is suggested that the combined hormonal and metabolic alterations of diabetes and hypertension reinforced one another in these spontaneously hypertensive rats, leading to intense stimulation of the hypothalamic-pituitary-adrenal system, the exacerbation of those cardiovascular degenerative changes known to be associated with uncontrolled diabetes or hypertension, eventual impaired adrenocortical steroidogenesis, hypotension and death.

Aldosterone↗
PubMed1977

Retardation in the development of spontaneous hypertension in SH rats by gonadectomy.

Young normotensive, male and female rats which develop hypertension spontaneously as they mature were gonadectomized when they were 30 days old. With time, intact controls and sham-operated controls showed a progressive increase in their blood pressure, attaining systolic pressure levels of 180 to 200 mm Hg when they were 120 days old. During this same period, the gonadectomized animals manifested a slight increase in blood pressure without becoming hypertensive. In keeping with their normotensive levels, the gonadectomized rats did not develop any cardiac or renal enlargement. Orchiectomy was associated with retardation of growth, an increase in the ratio of adrenal weight/body weight, concomitant with increased circulating levels of DOC in males vs. reduced DOC levels in females. There was no change in aldosterone levels in either sex. Cmpd. B levels were increased in the gonadectomized males and were slightly reduced in the gonadectomized females. The changes in Cmpd. B, DOC, and aldosterone in these gonadectomized animals cannot account for the inhibition of the spontaneously developing hypertension.

Adrenal Glands↗
PubMed1976

Effects of hypophysectomy on alloxan-diabetic, arteriosclerotic, breeder vs. non-arteriosclerotic, virgin rats.

A single s.c. injection (10 mg/100 g bw of alloxan) was given to nonarteriosclerotic, virgin, Sprague--Dawley rats and to breeder rats with preexisting arteriosclerosis, hyperlipidemia and hyperglycemia. All of the animals promptly developed severe diabetes with ketosis, hyperglycemia, and hyperlipidemia. Insulin therapy was deliberately withheld. Mortality was high. Seven days later one group was subjected to hypophysectomy and 30 days later, all of the animals were autopsied. The diabetes + hypophysectomy animals maintained their body weight better, did not have hypertrophied adrenal glands, showed the least elevation of serum enzymes, e.g., CPK, SGOT, SGPT and LDH, less hyperlipidemia and hyperglycemia and reduced corticosterone production than the animals with untreated severe diabetes. Despite the relative amelioration of metabolic derangements prognostic of cardiovascular degenerative changes, the diabetes + hypophysectomy animals manifested extensive renovascular damage and the breeder rats with pre-existing arteriosclerosis showed definite exacerbation of their arterial disease in response to the severe alloxan diabetes regardless of hypophysectomy. It is suggested that although hypophysectomy may alleviate certain metabolic derangements attributed to growth hormone, ACTH and adrenal steroids, the angiopathic damage proceeds inexorably.

Adrenal Cortex Hormones↗
PubMed1976

Arterial lesions in repeatedly bred spontaneously hypertensive rats.

Repeatedly bred male and female rats of many strains develop hyperglycemia, hyperlipidemia, hypertension, and arteriosclerosis spontaneously. The intensity of their arterial disease and related metabolic derangements appear to be related to their reproductive activity. Repeatedly bred spontaneously hypertensive rats (SHR) were found to have severe hypertension, hyperglycemia, hyperlipidemia, elevated creatine phosphokinase (CPK), serum glutamic oxaloacetic and glutamic pyruvic transaminase (SGOT, SGPT), and lactic dehydrogenase (LDH), as well as high circulating corticosterone levels. Despite these atherogenic metabolic derangements and their severe hypertension, the breeder SHR did not develop the severe, generalized arteriosclerosis found in other strains of breeder rats. Instead, the arterial lesions, consisting of intimal hyalinization and fibrosis, medial hypertrophy, and occlusion of the lumen, were found only in male breeder SHR and were confined to the intratubular arteries of the testes. It is suggested that the severe hypertension, genetic influences, or differences in hypothalamic-pituitary-adrenal-gonadal function in breeder SHR may not have been conducive to the development of arteriosclerosis in this particular strain of rats.

Adrenal Glands↗
PubMed1976

Hemodynamic changes in arteriosclerotic vs. non-arteriosclerotic rats during the acute stages of myocardial infarction.

Non-arteriosclerotic (virgin), male and female, Sprague-Dawley rats and arteriosclerotic (breeder), male and female rats were subjected to an acute myocardial infarct when injected with two subcutaneous doses of isoproterenol. Female rats, especially female breeder rats with advanced arteriosclerosis, survived their infarcts in superior fashion to male rats or those with the least severe arterial disease. Animals with severe arteriosclerosis showed the least loss of body weight and greatest increase in heart weight on Day 3 when cardiac necrosis reaches its zenith. Blood pressure and pulse pressure was most seriously reduced in animals with no or early arteriosclerosis only, being best maintained in the animals with the most severe arterial disease. Heart rate was not greatly altered in any of the various groups. Ventricular function, i.e., cardiac output, stroke volume, cardiac index, and left ventricular minute work, was severely impaired in the non-arteriosclerotic animals and in those with the least arterial disease. Total peripheral resistance was also least elevated and myocardial contractile strength (peak flow and max dF/dt) was greatest in female breeders with the most advanced arterial disease. Most intriguing, is the seemingly paradoxical but consistent finding that female breeders which develop the most severe arterial disease are able to best maintain cardiac function during the acute stress of myocardial ischemia.

Animals↗
PubMed1976

Comparative effects of cortisone, dianabol and enovid on isoprenaline-induced myocardial infarction in arteriosclerotic vs nonarteriosclerotic rats.

Male and female nonarteriosclerotic (virgin) and arteriosclerotic (breeder) Sprague-Dawley rats were subjected to acute myocardial infarction with isoprenaline. When myocardial necrosis was most intense, animals were given cortisone (high and low doses), Dianabol, or Enovid. Animals receiving large doses of cortisone manifested the best survival rate during the early stages of myocardial infarction. Although their serum enzyme levels were least elevated and their hearts showed tha least amount of damage, these animals had undergone the most intense body weight loss and began to die suddenly during the later stages of the experiment. These animals also manifested hyperlipidaemia, hyperglycaemia, septicaemia, severe disuse atrophy of their adrenal glands, and reduced Cmpd. B production. Animals treated with low doses of cortisone or with the anabolic and androgenic steroid, Dianabol, manifested none of the myocardial pretective effects of the larger dose of cortisone. These animals displayed a high incidence of left ventricular aneurysm formation concomitant with extensive cartilaginous metaplasia within the aneurysmal sites. Treatment with the contraceptive drug, Enovid, caused body weight loss, hyperlipidaemia, hyperglycaemia, gonadal atrophy and reduction of Cmpd. B production. Although the high dose of cortisone exercised definite salutary effects during early myocardial infarction, chronic treatment led to adrenal disuse atrophy and hypoadrenocorticism associated with sudden death during the later stages of myocardial repair. These findings indicate that proper adjustment of the dose and chronicity of corticosteroids used for treating the crisis of acute myocardial infarction must be made in order to provide effective protection against untoward pathophysiological conditions, acceleration of myocardial repair, but without suppression of adrenal function.

Adrenal Glands↗
PubMed1976

Aortic prolyl hydroxylase and the development of arteriosclerosis in the female breeder rat.

Female breeder rats develop arteriosclerosis spontaneously. The primary lesions seen in the early stages of the disease consist of subintimal and adjacent medial ground substance accumulations. With repeated breeding there is extensive elastolysis and calcification in the aorta. In aortae with developing arterial disease, prolyl hydroxylase activity is elevated as is both aortic protein and hydroxyproline, indicative of increased collagen deposition associated with the sclerotic degeneration. As the disease becomes very severe, however, prolyl hydroxylase activity declines, possibly associated with decreased metabolic activity in the severely calcified aorta. Lactation, followed by forced weaning, may condition the development or arterial disease through effect on collagen metabolism. During the first breeding cycle, aortic prolyl hydroxylase activity is elevated for 5 to 10 days after weaning. This increased collagen metabolism in the aorta may be a primary event in the development of the advanced calcific lesions characteristic of the lesions in breeder rats, and may be affected by hormones associated with different phases of the reproductive cycle.

Animals↗
PubMed1975

Metabolic and histopathologic changes in arteriosclerotic versus nonarteriosclerotic rats following isoproterenol-induced myocardial infarction with superimposed diabetes.

Male and female, arteriosclerotic and nonarteriosclerotic rats were subjected to acute myocardial infarction by two, subcutaneous injections (spaced 24 hr apart) of isoproterenol. During the immediate postinfarct repair phase all of the experimental animals were made severely diabetic with alloxan. Two weeks later the animals were sacrificed and their blood and pertinent organs analyzed for biochemical and pathologic changes. Females survived the myocardial infarct with superimposed diabetes in significantly greater than males. In addition to marked loss in body weight all of the experimental animals developed marked adrenal hypertrophy and thymus gland involution, cardiac hypertrophy, and unusual increase in ovarian or testicular size and weight. The combined conditions of myocardial infarction + diabetes led to substantial increases in serum creatine phosphokinase (CPK) and glutamic oxaloacetic transaminase (SGOT) whereas the enzymes glutamic pyruvic transaminase (SGPT) and lactic dehydrogenase (LDH) were reduced. Although serum triglyceride levels were greatly elevated, total cholesterol and free fatty acids were reduced. All of the animals were severely hyperglycemic and had greatly increased B.U.N. levels. Diabetes caused hypercalcemia but diabetes + myocardial infarction was associated with a definite reduction of this hypercalcemia. Despite marked adrenal hypertrophy, circulating Cmpd. B levels were subnormal. The diabetic condition and its attendant hyperlipidemia did not alter the morphologic nature of the arterial lesions in the breeder rats but the diabetes did cause definite impairment of the usual myocardial repair process observed in these rats with a particularly high incidence of left ventricular aneurysms in males.

Acute Disease↗
PubMed1975

Prolyl hydroxylase and collagen metabolism after experimental mycardial infarction.

Mature male Sprague-Dawley rats were subjected to an isoproterenol-induced myocardial infarction. Animals were sacrificed on a daily basis in order to assess the temporal changes in prolyl hydroxylase activity and collagen metabolism during the acute stages of myocardial necrosis and repair. Total myocardial hydroxyproline, as an indexof collagen content, increased promptly and markedly, beginning on day 4, and remained elevated thereafter. The incorporation of (14Cl)-proline into definitive hydroxyproline of mature collagen was also increased. The activity of the enzyme prolyl hydroxylase, which regulates the rate of conversion of proline to hydroxyproline in collagen, was elevated by day 2, remained high through day4, and then declined to a relatively constant but still slightly elevated level throughout the period of repair. It is believed that changes in these parameters of collagen metabolism reflect changes in myocardial fibroblastic cell and ground substance pertinent to fundamental aspects of repair of the injuried myocardium.

Animals↗