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Biomedical subjects

B C Wexler

Publications and source records attributed to B C Wexler.

At least 55 records · Page 3Linked to original sources
PubMed1980

Transplantation of pituitary and adrenal glands of spontaneously hypertensive rats into hypophysectomized or adrenalectomized, normotensive Sprague-Dawley rats.

Pituitary and adrenal glands removed from male and female spontaneously hypertensive (SH) rat donors with high blood pressure were implanted in normotensive, Sprague-Dawley (S-D) recipients which had been hypophysectomized or adrenalectomized. The transplants were accepted readily and after 90 days the animals were necropsied. Maintenance of organs and body weights suggested that the pituitary glands of SH rats have an adequate content of growth hormone but there may be an intrinsic deficiency of gonadotrophic hormones in this strain. The blood pressure of the hypophysectomized and adrenalectomized recipients was well maintained, particularly by the Sh-rat adrenal transplants, but the blood pressure of the recipients did not become abnormally elevated. SH-rat pituitary and adrenal glands caused fatty infiltration of the liver and hyperlipidaemia indicative of a lipotrophic factor in the SH rat strain. The histopathological changes in the transplanted pituitary and adrenal glands, and in intact pituitary and adrenal glands of the recipients, suggested that SH-rat pituitary glands secrete extra quantities of ACTH, that the pituitary-adrenal axis of this strain is extra sensitive to stressful stimuli, and that the spectrum of adrenal steroids secreted by this strain may be different from that of most normotensive strains.

Adrenal Glands↗
PubMed1979

Effect of CCL4-induced cirrhosis on the pathophysiologic course of acute myocardial infarction in nonarteriosclerotic vs arteriosclerotic male rats.

Arteriosclerotic and nonarteriosclerotic rats were treated with carbon tetrachloride (CCL4) to induce cirrhosis of the liver. Massive myocardial infarction was then induced in intact and CCL4-treated animals. During acute necrosis (Days 1 thru 3), animals were killed at 4, 8, 12 and 24 h on Days 1 and 2, and during myocardial repair on Days 4, 5 and 8. During the induction of cirrhosis, animals developed polydypsia, polyuria, and hyperglycemia; during myocardial infarction, the arteriosclerotic + cirrhotic animals developed severe and persistent congestive heart failure, i.e., hydrothorax. Adrenal and thymus gland weights and corticosterone levels indicated that cirrhosis per se increased pituitary--adrenal activity, particularly in arteriosclerotic animals. Enzyme levels of SGOT and SGPT demonstrated severe hepatic damage due to cirrhosis and acute myocardial infarction. Blood triglycerides and cholesterol responded abnormally in cirrhotic animals during acute myocardial ischemia due to their entrapment within hepatic cells. The cirrhotic animals manifested poor myocardial repair with persistent foci of necrosis, calcification, and a high incidence of large, occlusive, atrial thrombi. It is suggested that cirrhosis interferes with lipid metabolism and adrenal steroid conjugation leading to abnormal levels of mineralocorticoids which favor congestive heart failure, poor myocardial repair, and atrial thrombosis.

Alanine Transaminase↗
PubMed1979

Spontaneous arteriosclerosis in old, male, virgin Sprague--Dawley rats.

Virgin, male, Sprague--Dawley rats were observed from 3 to 34 months of age. Systolic blood pressure rose progressively with age, reaching abnormally elevated levels in some, becoming abnormally low in others. The old virgin males gained and then lost weight progressively with age, their pituitary and adrenal glands were heavier than young rats, and their thymi were greatly involuted. The old virgin rats manifested fatty infiltration of the liver and islet beta cell degranulation concomitant with hyperlipidemia, hyperglycemia, and elevated circulating corticosterone levels. Spontaneous arteriosclerosis, identical to that found in younger breeder rats was found in these old virgin males. Therefore, the vascular and other degenerative changes found in young breeder rats in considered to be an example of accelerated arterial disease.

Aging↗
PubMed1979

Opposing effects of deoxycorticosterone and spironolactone on isoprenaline-induced myocardial infarction.

Adult, male Sprague-Dawley rats were subjected to massive myocardial infarction with isoprenaline. Some of the animals were treated with the potent mineralocorticoid, deoxycorticosterone, or the anti-mineralocorticoid, spironolactone. Autopsies spaced at sequential time intervals demonstrated that circulating levels of enzymes, eg, CPK, SGOT, SGPT and LDH, lipids, eg, triglycerides, free fatty acids, and cholesterol, glucose, Bun, and corticosterone rose in conjunction with on-going necrosis and became lowered in conjunction with myocardial repair. Body and organ weights, ie, adrenal, thymus, heart, and kidney, underwent dynamic changes commensurate with necrosis and repair. Animals given isoprenaline alone died (52% survival) during the height of their massive infarct and congestive heart failure (Days 3 and 4). Animals treated with DOC showed the most severe congestion but died (36% survival) during the late repair phase (Days 7 and 8). Animals treated with spironoloactone showed the most effective clearance of thoracic fluid and also dies (18% survival) during the late repair phase (Days 7 and 8). These spironolactone-treated animals had large, left ventricular aneurysms with organised, adherent thrombi. It is believed that alterations in electrolyte balance induced by DOC or spironolactone caused changes in adrenocortical function which greatly modified the usual pathophysiological response to myocardial infarction.

Animals↗
PubMed1979

Isoprenaline-induced myocardial infarction in spontaneously hypertensive rats.

Spontaneously hypertensive rats were subjected to massive myocardial infarction. The pathophysiological changes were similar to those of normotensive rats but the spontaneously hypertensive rats developed congestive heart failure during myocardial repair rather than during the necrosis phase and survived in superior numbers. Blood pressure fell despite maximally increased corticosterone levels. Atrial and ventricular thromboses and left ventricular aneurysm formation were frequent.

Animals↗
PubMed1979

Effect of gonadectomy on isoproterenol-induced myocardial infarction.

Adult male and female Sprague-Dawley rats were subjected to an isoproterenol-induced myocardial infarction. Six weeks before the induction of myocardial infarction, some of the animals had been orchiectomized or ovariectomized. The animals were autopsied at regularly timed intervals on days 1, 2, 3, 8, and 15 after myocardial infarction. The gonadectomized animals manifested less severe untoward changes, survived in greater numbers, and experienced superior repair of their damaged hearts. Circulating levels of enzymes (e.g., CPK, GOT, GPT, and LDH), lipids, glucose, and BUN rose and fell during the acute necrosis and repair phases with distinct differences between the intact and castrated animals. Reciprocal changes in the weight of the adrenal and thymus glands, coupled with dynamic changes in circulating corticosterone levels, reflected marked temporal changes in the spectrum of adrenal steroids being secreted, as well as gonadal hormone mediated changes affecting adrenocortical function. The implications of these findings are that adrenocortical, androgenic, and estrogenic hormones condition the nature of the pathophysiologic response to acute myocardial infarction in rats.

Adrenal Glands↗
PubMed1979

Detection of early myocardial infarction by radioimmunoassay of myoglobin.

A newly devised radioimmunoassay for the measurement of myocardial myoglobin has been modified by us to measure circulating myoglobin levels in rats subjected to isoproterenol-induced myocardial infarction of various degrees of severity. The method has been found to be very effective. Myoglobinemia proved to be a sensitive index of early myocardial damage in rats, perhaps superseding the enzyme CPK in detecting early myocardial damage. Both myoglobin and CPK were equally effective in providing an index of the extent of histopathologic myocardial infarction. The changes in myoglobin and CPK did not correlate well with the changes in plasma SGOT, SGPT, and LDH, which are more diagnostic of the later stages of acute myocardial infarction. Myoglobinemia offers excellent promise as a diagnostic aid in detecting early myocardial infarction in rats, and perhaps ultimately in humans, since there are only small differences between the immunologic specificity of human versus rat myoglobin.

Alanine Transaminase↗
PubMed1979

Aldosterone, deoxycorticosterone, corticosterone, and prolactin changes during the lifespan of chronically and spontaneously hypertensive rats.

Male and female spontaneously hypertensive rats (SHR), which develop hypertension spontaneously with maturation, were autopsied at select time intervals from weaning to 28 months. Their blood pressure began to rise steeply at 4--5 weeks, reaching a zenith of 180--240 mm Hg after 4 months. Elevated blood pressures were maintained in both sexes. After 20 months, the male SHR began to die of myocardial infarction and hypotensive crisis. Heart and adrenal gland weight increased progressively not only during the phase of rapidly rising blood pressure but also during the period of plateaued but sustained high blood pressure. RIA of plasma levels of aldosterone, deoxycorticosterone, corticosterone, and PRL, under both quiescent and mildly stressful conditions, demonstrated that the pituitary-adrenal axis of SHR progressively increases its propensity to respond to stress with maturation. This capacity to respond to stress was maintained despite the severe high blood pressure and the attainment of relative old age, i.e. 2 yr. An incremental change in circulating PRL, corticosterone, and aldosterone as early as 2 months of age, when blood pressure levels are beginning to rise, suggests that there may be some connection between the genetically programmed pathogenesis of the spontaneous hypertension and the progressively increasing (with age) sensitivity of the pituitary-adrenal axis to stress.

Aging↗
PubMed1979

Inhibition of the development of spontaneous hypertension in SH rats by gonadectomy or estradiol.

Young male and female rats that become spontaneously hypertensive when they mature were gonadectomized at 30 days of age while they were still normotensive. Gonadectomy retarded the usual steep ascent of blood pressure up to 120 days of age. Ovariectomized females "escaped" from this inhibiting effect, and blood pressure rose to severely high levels, i.e., 210 mm Hg, from 150 to 240 days. Treatment with testosterone or estradiol demonstrated that estradiol was particularly effective in inhibiting the usual rise in blood pressure in intact (sham-operated) or gonadectomized males and females. Although effectively lowering blood pressure, estradiol also caused increased pituitary and adrenal weights, hyperlipidemia, and increased circulating levels of corticosterone and DOC.

Adrenal Glands↗
PubMed1979

Diverse cardiovascular responses to aortic constriction in normotensive Sprague-Dawley versus spontaneously hypertensive rats.

Normotensive, Sprague-Dawley (S-D) and spontaneously hypertensive (SH) rats were subjected to aortic ligature. The systolic blood pressure of S-D rats was increased by +/- 80 mm Hg, whereas the blood pressure of SH rats with pre-existent hypertension increased only slightly, +/- 9 mm Hg. The S-D rats developed myocardial and renal infarcts as well as polyarteritis nodosa; the SH rats developed testicular and microadrenocortical infarcts only. Aortic-ligated S-D rats had elevated creatine phosphokinase, serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase, and lactic hydrogenase levels and manifested hyperglycemia, hypercholesterolemia, and elevated blood urea nitrogen (BUN) levels. Corticosterone levels increased in aortic-ligated S-D rats but decreased in SH rats. Collateralization about the site of aortic ligature appeared to be the same in both strains. It is suggested that the acutely induced hypertension in S-D rats rather than SH rats and differences in adrenal steroidogenesis between the two strains would best account for the dichotomous cardiovascular response to aortic constriction.

Adrenal Cortex↗
PubMed1979

Myocardial infarction in spontaneously hypertensive rats with superimposed adrenal-regeneration hypertension.

The elevated blood pressure of spontaneously hypertensive rats (SHR) was further exacerbated by subjecting these animals to surgically induced adrenal-regeneration hypertension (ARH). When chronic abnormally high blood pressure had been in effect for 12 weeks, the animals were subjected to an acute and massive myocardial infarction with isoprenaline. Hypertensive but intact SHR survived better than ARH-treated animals. Circulating enzyme (CPK, SGOT, SGPT and LDH), lipid and glucose levels and BUN manifested much greater excursions commensurate with more extensive myocardial infarction in ARH-treated than in intact SHR. ARH-treated SHR displayed a high incidence of atrial and ventricular thrombi associated with frequent left ventricular aneurysm formation. It is suggested that the more extensive myocardial connective tissue and ground-substance degeneration in ARH-treated SHR is due to the impoverished steroidogenic capacity of their regenerated adrenal glands.

Adrenal Glands↗
PubMed1979

Arterial lesions and hypertension induced by saline, unilateral nephrectomy, and deoxycorticosterone in spontaneously hypertensive SHR rats.

Male and female, 100 days old, spontaneously hypertensive rats (SHR) were divided into two major groups: intact and uninephrectomized, given either no treatment, 1p.100 saline drinking water, 1p.100 saline + Deoxycorticosterone (DOC), or DOC alone. The DOC (Percorten pivalate) was given subcutaneously 2 times weekly, at a dose level of 2 mg/rat for 8 weeks. At autopsy, the combination of DOC + saline caused: the greatest exacerbation of blood pressure, marked catabolism, adrenal hypertrophy and thymic involution, little increase in heart weight, but a marked increase in kidney weight, elevated triglyceride and free fatty acids, cerebral and myocardial necrosis, fibrinous hyalinization of the cerebral, coronary, mesenteric, renal, testicular and ovarian arteries, foci of aortic cartilaginous metaplasia, PAN, foci of hepatic necrosis, and extensive lipid depletion from the zonae glomerulosa. Circulating corticosterone levels were suppressed to below normal levels. Excursion of circulating CPK levels coincided with the finding of myocardial necrosis and cerebral damage. It is suggested that the genetically-mediated hypertension of SHR is programmed through abnormal activity of the hypothalamic-pituitary axis and the specific morphologic make-up of arterial lesions is dependent upon the variety of adrenal or gonadal steroids secreted and their conditioning effect on the arterial wall.

Animals↗
PubMed1978

Myocardial infarction in young vs old male rats: pathophysiologic changes.

Young (90 days) and old (15 months) male, Sprague-Dawley rats were subjected to an acute and massive myocardial infarct by giving them two injections of a large dose of isoproterenol. The animals were autopsied at sequential time intervals to ascertain the similarities or dissimilarities in the pathophysiologic events which attend acute myocardial infarction and repair in young vs old rats. Although the signs and severity of hypotensive shock appeared to be equal, mortality was higher in the old rats, especially during the acute necrosis phase. The older rats also manifested more severe and persistent congestive heart failure, i.e., hydrothorax. Serum enzymes (CPK, SGOT, SGPT, and LDH), lipids (triglycerides, free fatty acids, and cholesterol), glucose, and BUN levels manifested a dynamic rise and fall concomitant with the induced myocardial necrosis and repair phases with distinct differences in these metabolic changes between young and old rats. Despite initially higher circulating levels of corticosterone in the old vs young rats, the older animals manifested little or no increase in circulating corticosterone levels during the acute stress of myocardial infarction. This apparent lack of adrenocortical responsiveness was accentuated by the concomitant finding of greatly hypertrophied, hemorrhagic, and lipid-depleted adrenal glands in the old rats vs a dynamic increase in circulating corticosterone levels and alterations in the weight of adrenal and thymus glands of the young rats. During the myocardial repair phase, the young rats manifested extensive endocardial fibrosis whereas the old rats displayed little or no endocardial fibrosis but copous and persistent myocardial edema and ground substance in keeping with their higher concentration of cardiac hexosamine. The pathophysiologic course of events which attends myocardial necrosis and repair is quite different in young vs old rats and may be related to the degree of responsiveness of the pituitary-adrenal axis which changes with age.

Adrenal Glands↗
PubMed1978

Clofibrate retardation of naturally-occurring arteriosclerosis in repeatedly-bred male and female rats.

Repeatedly-bred, male and female Sprague-Dawley rats which develop hyperglycemia, hyperlipidemia, hypertension, and arteriosclerosis spontaneously were killed at sequential time intervals, i.e., when the females had completed 1, 2, 3 and 4 pregnancies. The control breeders received no treatment; the experimental animals were given 113 mg of clofibrate/100 g of b.w., subcutaneously, daily, 5 times per week. Clofibrate-treated breeders manifested reduction in blood pressure and in the incidence and severity of arterial disease characteristic of repeatedly-bred rats. The aortic lesions of the clofibrate-treated breeders showed attenuation of the usual severe ground substance alterations, the degenerative changes in connective tissue elements, e.g., fibrosis and elastosis, and absence of calcification and cartilaginous metaplasia. Clofibrate-treated breeders did not show any unusual elevation in serum enzymes, e.g., CPK, SGOT, SGPT and LDH, or significant reduction of their hyperlipidemia. They manifested a definite reduction in adrenocortical and medullary histopathology and their circulating corticosterone levels were subnormal compared to non-treated breeders. It is suggested that the protective effect of clofibrate was mediated through its ability to block normal adrenal steroidogenic pathways rather than through its antilipemic action.

Adrenal Cortex↗
PubMed1978

Protective effects of clofibrate on isoproterenol-induced myocardial infarction in arteriosclerotic and non-arteriosclerotic rats.

Male and female, arteriosclerotic and non-arteriosclerotic rats were treated with the anti-lipemic agent, clofibrate, for 8 days and then subjected to an acute myocardial infarction by injecting them with two large doses of isoproterenol spaced 24 hours apart. The animals were killed at sequential time intervals during the acute necrosis and early repair phases of myocardial infarction. Pre-treatment with clofibrate caused a definite improvement in survival, less shock and prostration, and ECG evidence of little or no ischemia. Increased SGOT levels, hepatic lipid and necrosis were indicative of advanced liver damage. Although clofibrate-treated animals showed little change in serum lipids during the acute cardiac necrosis phase, they were hyperglycemic and showed the greatest increase in BUN levels. Clofibrate-treated animals had higher serum corticosterone levels than those given isoproterenol alone. Despite superior survival rates, both the arteriosclerotic and non-arteriosclerotic, clofibrate-treated animals exhibited equally severe histopathologic evidence of myocardial damage. It is suggested that the protective effect of prophylactic treatment with clofibrate against isoproterenol-induced myocardial infarction in rats may be due to its ability to change corticosterone levels in the circulation.

Alanine Transaminase↗
PubMed1978

Pathophysiological differences between paired and communal breeding of male and female Sprague-Dawley rats.

Sexually mature, male and female Sprague-Dawley rats were housed in large communal breeding cages or in smaller paired breeding cages. Virgin control rats of the same age were housed similarly but segregated by sex. Breeders became obese, developed a fatty liver, and showed elevated levels of triglycerides, free fatty acids, and cholesterol. Breeders had high blood pressure, enlarged hearts, hyperglycemia, and islet beta cell degranulation. Serum enzymes, creatine phosphokinase, serum glutamic oxalo-pyruvic transaminase, serum glutamic pyruvic transaminase, lactate dehydrogenase, and blood urea nitrogen levels were elevated in breeder rats. The adrenal glands of male breeders appeared hyperactive; the adrenal glands of female breeders were thrombosed and appeared to be hypoactive. Male breeder rats developed microscopic aortic lesions only; female breeders developed advanced calcific aortic sclerosis. Male breeders kept in active stud service manifested the most abnormal metabolic and pathophysiological changes. Female breeders developed similar pathophysiological changes after four pregnancies, irrespective of their paired or communal breeding environment. Virgin rats were normal regardless of housing conditions. Our findings suggest that repeated breeding in male and female rats causes resetting of the hypothalamic-pituitary-adrenal-gonadal axis. This may lead to disturbed hormonal and metabolic changes which culminate with the development of accelerated cardiovascular degenerative changes.

Adrenal Cortex↗