John P. McMurtry

Effects of bromocryptine on hormone and blood pressure levels in the spontaneously hypertensive rat.

Summary Treatment of young and old male and female SH rats with bromoergo-cryptine (21 days) significantly reduced blood prolactin concentrations. Blood pressure was slightly depressed in young male SH rats whereas in females blood pressure was unchanged. Hypertension was reduced (30%) to normotensive levels in old rats of both sexes. Corticosterone levels were slightly affected by treatment. A significant drop in aldosterone levels was noted in young male SH rats exclusively. The hypotensive action of bromocryptine (a dopamine agonist) is uncertain but may be related to changes in catecholamine levels or actions within the central nervous system.

Dexamethasone suppression of Cushingoid degenerative changes in obese spontaneously hypertensive rats (SHR)

Male and female, young (2 months old) and mature (10 months old), obese and nonobese, spontaneously hypertensive rats (SHR) were treated with dexamethasone, 5 micrograms/rat and 10 micrograms/rat, respectively, subcutaneously (SC) 2 times daily for 5 months. Steroid treatment stilled the voracious appetite of the obese SHR, and the massively obese, mature animals were reduced to almost normal size. The young, steroid-treated, obese SHR did not develop their genetically programmed corpulency. The untreated, young and mature, obese SHR ate voraciously, became massively obese, and developed their characteristic Cushings disease-like spectrum of degenerative changes, eg, hypertension, hyperlipidemia, hyperglycemia, muscle wasting, kidney stones, thin skin, and accelerated aging. The blood pressure of the steroid-treated animals was lowered concomitant with reduced levels of circulating ACTH, beta endorphin, insulin, triglycerides, and cholesterol. Dexamethasone caused hyperlipidemia, hyperglycemia, and increased BUN levels in young obese and nonobese SHR only. The mature obese SHR had giant-sized thymus glands that were further enlarged with steroid treatment; dexamethasone was thymolytic in young, obese and nonobese SHR. Dexamethasone caused severe reduction of pituitary and adrenal gland size, simulating the condition of hypophysectomy. These findings demonstrate that dexamethasone suppression of the pituitary-adrenal axis palliates and prevents the spontaneous development of Cushingoid degenerative changes in these genetically obese and hypertensive rats.

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. Myo globinemia offers excellent promise as a diagnostic aid in detecting early myo cardial infarction in rats, and perhaps ultimately in humans, since there are only small differences between the immunologic specificity of human versus rat myoglobin.

Circadian rhythm of circulating corticosterone and prolactin levels in spontaneously hypertensive rats

Abstract Circulating levels of corticosterone and prolactin were measured by radioimmunoassay at hourly intervals during a 24 h period to establish the diurnal rhythm of these hormones in spontaneously hypertensive rats (SHR). Corticosterone levels exhibited a distinct circadian variation with concentrations reaching a zenith at 2000 h and a nadir at 1200 h in male and female SHR. Corticosterone levels in females were consistently greater than males. Circulating prolactin levels were greater during the light h than dark in the female; the opposite occurred in males. Measurement of pituitary prolactin content tended to be low when serum prolactin levels were high and vice versa. The circadian rhythm of circulating corticosterone and prolactin in the hypertensive SHR was found to be similar to the day-night patterns established for normotensive rats. However, these measurements were made under quiescent conditions. It is suggested that because SHR are hyper-responsive to stress and because corticosterone and prolactin have synchronous effects on stress-induced adrenal steroidogenesis, further investigation of prolactin and corticosterone may reveal a participatory role of these hormones in the pathogenesis of the genetically-programmed hypertension of SHR.

Circadian rhythm of circulating glucose, insulin and growth hormone in spontaneously hypertensive rats

Abstract Circulating levels of growth hormone (GH), insulin, and glucose were measured at hourly intervals during a 24 h period to establish the diurnal rhythm of these hormones in spontaneously hypertensive rats (SHR). There was no statistically significant correlation between circulating GH levels and pituitary GH content. Serum GH appeared to be higher at night in female SHR and higher during day-light hrs in male SHR. GH levels fluctuated considerably, whereas insulin levels showed much less diurnal variation. Although there was no statistically significant correlation between blood glucose and insulin levels, glucose levels rose and fell considerably during the 24 hr period with a definite decline in blood glucose during the nocturnal hyperactivity observed in SHR. These findings are of interest in that SHR have giant-sized islets of Langerhans, develop hyperglycemia spontaneously, and are growth-retarded compared to most normotensive strains of rat.

Hyperprolactinemia and Hyperadrenocorticism Accompanied by Normal Blood Pressure in Sprague-Dawley Rats

Abstract Pituitary glands removed from adult female normotensive Sprague-Dawley (S-D) rats were implanted beneath the renal capsule of 100-day-old 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 prior 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.

Propranolol-induced alterations in the pathophysiology of spontaneously hypertensive rats

Abstract Male and female, spontaneously hypertensive rats (SHR) were treated with propranolol (14 weeks) when they became 1, 4 and 8 months old prior to, during the steep ascent, and when severe high blood pressure becomes established. Propranolol prevented the usual increase in blood pressure at an early age but did not effectively lower blood pressure at all age levels. Propranolol-treated SHR manifested marked alterations in pituitary, adrenal, thymus, heart and gonadal weights. Despite progressively increasing hyperlipidemia and hyperglycemia, there were no significant differences between lipid, glucose, BUN, or serum enzyme levels in treated vs nontreated SHR. Circulating aldosterone and corticosterone levels were reduced in propranolol-treated SHR. Male SHR, treated or untreated, developed severe cardiovascular-renal lesions when they became 8 months old; none of the female SHR manifested any pathologic changes. It is suggested that the anti-hypertensive effects of propranolol were partially mediated by hormonal as well as by hemodynamic mechanisms.

Circadian Rhythm of Circulating Aldosterone in Spontaneously Hypertensive Rats

Abstract Circulating levels of aldosterone were measured by radioimmunoassay at hourly intervals during a 24-hr period to establish the diurnal rhythm of this mineralo-corticoid in spontaneously hypertensive rats (SHR). Aldosterone levels exhibited a distinct circadian variation with concentrations reaching a zenith at 2000 hr and a nadir at 1200 hr in male and female SHR. Aldosterone levels in females were consistently greater than males. Nocturnal aldosterone levels were highest in the early morning hours in male and moderately elevated in female SHR. Male SHR have significantly higher blood pressure than female SHR.

Pregnancy vs Pseudopregnancy in the Induction of Hypertension and Arteriosclerosis in Sprague–Dawley Rats

Abstract Sprague–Dawley rats were subjected to either repeated breeding with a minimal amount of rest between pregnancies or to repeated pseudopregnancies induced by electrical stimulation of the uterine cervix. Representative numbers of animals from each of the two groups were killed after two, four, and six pregnancies or pseudopregnancies. The multiparous rats developed progressively increasing blood pressure; the blood pressure of pseudopregnant rats remained normal. The multiparous rats manifested progressively increasing adrenal, heart, and kidney weight accompanied by hyperlipidemia, i.e., triglycerides, free fatty acids, and cholesterol, hyperglycemia, and elevated BUN levels vs elevated free fatty acid levels only in pseudopregnant rats. None of the pseudopregnant rats developed aortic sclerosis, whereas the multiparous developed progressively worsening and virtually ubiquitous arteriosclerosis. It is suggested that although pseudopregnancy, like pregnancy, causes alterations in hypothalamic–pituitary function, the hormonal-metabolic conditions are not the same, e.g., absence of extraadrenal glandular activity. The hormonal–metabolic conditions entrained by pseudopregnancy are not conducive to the development of the cardiovascular degenerative changes associated with repeated pregnancy.