Biomedical subjects

R McCarty

Publications and source records attributed to R McCarty.

At least 73 records · Page 4Linked to original sources

PubMed1987

Accelerated development of cardiac sympathetic responses in spontaneously hypertensive (SHR) rats.

The functional development of cardiac and adrenal medullary responses to reflex activation of the sympathetic nervous system was studied in preweanling spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) normotensive rats. Pups of the two strains received injections of insulin or saline at 2, 4, 8, 12, or 16 days of age and were sacrificed 3 h later. Insulin administration produces a significant decrease in circulating levels of glucose which in turn results in a centrally mediated increase in sympathetic outflow. The induction of ornithine decarboxylase (ODC) in heart and the depletion of epinephrine from the adrenal medulla served as tissue markers of functional sympathetic neurotransmission. WKY and SHR pups had comparable levels of ODC activity in heart under basal conditions. In contrast, levels of catecholamines in the adrenals were greater in SHR pups at 2 and 4 days of age. Following insulin administration, SHR pups exhibited a greater induction of cardiac ODC activity at 2, 4, and 8 days of age compared to age-matched WKY controls. However, there were no differences between SHR and WKY pups in the magnitude of the adrenal medullary response to insulin-induced hypoglycemia. These alterations in sympathetic-target tissue development during the first postnatal week of life may contribute in part to the higher arterial pressures maintained by SHRs throughout the lifespan.

Adrenal Medulla↗

PubMed1987

Hypertension in SHR rats: contribution of maternal environment.

The role of the maternal environment in the development of hypertension in spontaneously hypertensive (SHR) rats was evaluated using the technique of reciprocal cross fostering. Litters of SHR and Wistar-Kyoto (WKY) normotensive pups were either reared by their natural mothers, in fostered to mothers of the same strain, or cross fostered to mothers of the opposite strain shortly after birth. Litters were weaned at 21 days of age, at which time all pups were weighed. At 18-20 wk of age, resting mean arterial blood pressures (MAP) and heart rates were determined for male subjects from the six groups (2 strains X 3 rearing conditions) via an indwelling tail artery catheter. At weaning, SHR animals weighed less than WKY animals. SHRs fostered to WKY mothers were significantly heavier than control SHRs, and WKYs fostered to SHR mothers were significantly lighter than WKY controls at weaning. These body weight differences were also evident in adulthood. Cross fostering SHR pups to normotensive WKY mothers resulted in a dramatic reduction in resting MAP measured in adulthood. Conversely, cross fostering WKY pups to SHR mothers had no measurable effect on adult resting MAP. We propose that an interaction between characteristics of the SHR maternal environment and a genetic susceptibility in SHR pups is essential in triggering the full expression of the hypertensive phenotype in this animal model of human essential hypertension.

Animals↗

PubMed1987

Alterations in binding sites for atrial natriuretic factor in kidneys and adrenal glands of Dahl hypertension-sensitive rats.

Binding sites for atrial natriuretic factor (ANF) were studied in kidneys and adrenal glands of 7- and 10-week-old male Dahl hypertension-sensitive (S/JR) and hypertension-resistant (R/JR) rats by quantitative autoradiography. Binding sites for 125I-ANF-28 in kidney were highly localized and of high density in the glomeruli; binding sites were less concentrated in the renal papilla. In adrenal gland, binding sites for 125I-ANF-28 were highly concentrated in the zona glomerulosa, but were of a very low density in the inner adrenal cortex. At 7 weeks of age, the maximum binding capacity (Bmax) for 125I-ANF-28 in kidney glomeruli was increased by 21% in S/JR rats compared with R/JR rats. From 7 to 10 weeks of age, decreases in Bmax for 125I-ANF-28 in glomeruli occurred, with no apparent difference between strains. Strain or age differences in the affinity constant (Ka) for 125I-ANF did not occur in the kidney. In adrenal zona glomerulosa, the Bmax for 125I-ANF-28 binding was similar for S/JR and R/JR rats at 7 weeks of age. At 10 weeks of age, however, Bmax for 125I-ANF-28 in adrenal zona glomerulosa was increased by 19% in S/JR rats compared with age-matched R/JR controls. These findings suggest that alterations may occur in ANF binding sites in kidney and adrenal gland of S/JR rats in response to the sharp increase in blood pressure that is characteristic of rats of this strain.

Adrenal Cortex↗

PubMed1986

Effects of dietary sodium on dopamine content of rat adrenal cortex.

Dopamine occurs in the adrenal cortex and appears to provide maximum tonic inhibition of aldosterone secretion. In the present experiments, the effects of high or low sodium (Na+) intake on concentrations of dopamine in the adrenal cortex of adult male Sprague-Dawley rats were examined. In the first experiment, sham-operated and adrenal demedullated rats were provided with 1.5% NaCl or tap water for drinking for 5 days. In the second experiment, sham-operated and adrenal demedullated rats were fed regular laboratory chow (approximately 0.45% NaCl) or low Na+ chow (0.001-0.005% NaCl) for 5 days. High Na+ intake was attended by dramatic increases in fluid consumption, urine production and Na+ excretion. However, high Na+ intake did not affect levels of dopamine, norepinephrine or epinephrine in the adrenal glands. Approximately 45% of adrenal dopamine but less than 4% of either norepinephrine or epinephrine was localized in the adrenal cortex. In the second experiment, animals fed a diet low in Na+ had a significant reduction in Na+ excretion but levels of adrenal catecholamines were unaffected. Approximately 36% of adrenal dopamine but less than 5% of either norepinephrine or epinephrine was localized in the adrenal cortex. These findings suggest that adrenal cortical dopamine concentrations remain relatively constant in spite of presumed differences in turnover rates of this neurohormone.

Adrenal Cortex↗

PubMed1986

Binding sites for atrial natriuretic factor (ANF) in brain: alterations in Brattleboro rats.

Binding sites for atrial natriuretic factor (ANF-28) were analyzed in discrete brain areas of Brattleboro rats with hereditary diabetes insipidus and Long-Evans (LE) controls by quantitative autoradiography. The maximum binding capacity (Bmax) and affinity constant (Ka) for 125I-ANF-28 were elevated significantly in the subfornical organ of Brattleboro rats compared to matched LE controls. In contrast, values for Bmax and Ka for 125I-ANF-28 binding in choroid plexus and area postrema were similar for rats of the two strains. These findings are consistent with a selective upregulation of ANF-28 binding sites in the subfornical organ of Brattleboro rats which exhibit a profound disturbance in body fluid homeostasis. These alterations in ANF-28 binding sites in the subfornical organ may represent a compensatory response to the absence of vasopressin in the Brattleboro rat.

Animals↗

PubMed1986

Age-related alterations in sympathetic-adrenal medullary responses to stress.

In mammals, aging is often viewed as a progressive decline in physiological competence with a corresponding inability to adapt to stressful stimulation. Several current theories of aging have implicated the sympathetic nervous system in many of the metabolic, cardiovascular and behavior changes which attend advancing age. To provide an empirical base for evaluating the role of the sympathetic nervous system in aging, I have studied the activity of the sympathetic nerves and the adrenal medulla of adult and aged Fischer 344 male rats before, during and after exposure to various stressful stimuli. Plasma levels of norepinephrine and epinephrine served as biochemical indices of the activity of the sympathetic nerves and the adrenal medulla, respectively. Under resting conditions, rats 4-24 months of age had similar plasma levels of both catecholamines. When stressed for a brief period of time (intermittent footshock for 1 min), 12- and 24-month-old rats exhibited a diminished sympathetic-adrenal medullary response compared to young adult rats (4 months old). With an increase in the intensity and duration of the stressor (cold water immersion for 10 min), the sympathetic-adrenal medullary responses of 6- and 22-month-old rats were comparable. However, the sympathetic nervous system remained in a heightened state of activity for a longer period of time following the stressful stimulus in aged rats. Finally, with prolonged exposure to an intense stressor (cellular glucoprivation following administration of 2-deoxy-D-glucose), 24-month-old rats exhibited an exaggerated adrenal medullary response and a greater mortality rate compared to 6-month-old rats. These findings suggest that homeostatic regulation of the sympathetic nervous system is impaired in aged rodents. Further, the nature of this impairment is dependent upon the intensity and duration of the activating stimulus. These apparent age-related alterations in regulation of the sympathetic nervous system may contribute to the increased morbidity and mortality of aged animals during prolonged exposure to stressful stimulation.

Adrenal Medulla↗

PubMed1986

Sympathetic nervous system development in hypertensive rats.

Adrenal Medulla↗

PubMed1985

Sympathetic-adrenal medullary and cardiovascular responses to acute cold stress in adult and aged rats.

In this study, adult (5 months) and aged (22 months) Fischer 344 (F-344) male rats were surgically prepared with chronic tail artery cannulae. Two days after surgery, rats were stressed by immersion in 12 degrees C water for 10 min. Blood samples (0.5 ml) were collected before and at timed intervals after cold immersion (0, 15 and 60 min) and were later assayed for content of norepinephrine and epinephrine. Consistent with earlier studies from this laboratory, there were no differences between ages in basal plasma levels of either catecholamine or in mean arterial pressure or core temperature. However, basal heart rates of aged rats were approximately 10% greater than values for adult rats. During cold immersion, aged rats had greater decrements in heart rate compared to adults but there were no age-related differences in mean arterial pressure or core temperature. Immediately following cold immersion, increments above basal values for plasma norepinephrine and epinephrine (4.2-4.6 and 11.8-14.1-fold, respectively) were similar for 5- and 22-month-old rats. However, in aged rats plasma norepinephrine was greater at 60 min post-immersion and plasma epinephrine was greater at 15 and 60 min post-immersion compared to values for adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗

PubMed1985

Unilateral odor deprivation: effects on the development of olfactory bulb catecholamines and behavior.

The present studies began an examination of the process by which unilateral odor deprivation results in a 25% reduction in the size of the olfactory bulb. Rat pups had a single naris occluded on the day after the day of birth (Day 1) and were tested at several early postnatal ages. Dopamine (DA) levels were measured to gauge the effects of deprivation on a transmitter system which is intrinsic to the bulb, while norepinephrine (NE) concentrations were assessed to determine how deprivation affects inputs to the bulb from higher brain regions. A significant reduction in DA concentration (pg/mg protein) was observed on Day 8 and persisted until Day 30 although protein concentrations (pg/mg bulb) were not affected. In contrast, deprivation did not significantly alter NE concentration. Deprived and control pups did not differ on a series of behavioral and morphometric measures, suggesting that the surgical procedure did not seriously impair normal growth patterns. The results indicate that unilateral naris occlusion induces rapid and specific changes within the olfactory bulb.

Animals↗

PubMed1985

Cardiovascular responses to acute footshock stress in adult and aged Fischer 344 male rats.

Tail artery catheters were surgically implanted in Fischer 344 male rats to allow for measurement of mean arterial pressure (MAP, mm Hg) and heart rate (HR, beats/min) in conscious, unrestrained rats. Basal values of MAP and HR were similar for groups of 4, 12 and 24 month old rats. Increments in Map did not differ among rats of the 3 ages following handling and transfer to a shock chamber or immediately or 5 minutes after exposure to inescapable footshock (2.0 mA, 0.6 sec duration, every 6 sec for 1 min). In contrast, there was a significant age-related attenuation of the tachycardia following handling and transfer of rats to the shock chamber and at the end of footshock. These data are consistent with previous findings of a reduced sensitivity of the aged myocardium to stress-induced sympathetic stimulation.

Aging↗

PubMed1985

Enhanced sympathetic-adrenal medullary response to cold exposure in spontaneously hypertensive rats.

To investigate the regulation of sympathetic-adrenal medullary function in spontaneously hypertensive (SHR) male rats, we measured urinary catecholamine excretion for 4 h at room temperature and also during cold exposure (4 degrees C) in groups of four and 12-week-old stroke-prone SHR (SHRSP), stroke-resistant SHR (SHRSR) and normotensive Wistar-Kyoto (WKY) rats. The effect of cold exposure on 12-week-old adrenal denervated rats was also examined. At room temperature, urinary excretion of epinephrine, but not norepinephrine or dopamine, was increased significantly in four-week-old SHRSP and SHRSR rats compared with age-matched WKY. The enhanced excretion of epinephrine at room temperature was not observed in hypertensive rats at 12 weeks of age. During cold exposure, urinary concentrations of each catecholamine increased markedly in rats of all three strains. In addition, the epinephrine response was significantly enhanced in SHRSP rats and the norepinephrine, epinephrine and dopamine responses were significantly enhanced in SHRSR rats. Following adrenal denervation, the urinary epinephrine response to cold exposure was abolished in all strains. These results reveal an enhancement of sympathetic and neurally-mediated adrenal medullary responses in prehypertensive SHR rats and a greater urinary epinephrine response to cold exposure in four and 12-week-old SHR rats. This alteration in catecholamine secretion may be important in the development and maintenance of this type of experimental hypertension.

Adrenal Medulla↗

PubMed1984

Effects of 2-deoxyglucose on plasma catecholamines in adult and aged rats.

To examine the effects of aging on the responsiveness of the sympathetic-adrenal medullary system, I have measured plasma levels of norepinephrine (NE) and epinephrine (EPI) in adult (6 months old) and aged (24 months old) Fischer 344 male rats. Two days prior to testing, rats were surgically prepared with chronic tail artery catheters to permit remote sampling of blood in conscious, unrestrained animals. Following collection of basal blood samples, each rat received a single injection of 2-deoxyglucose (2-DG, 250 or 500 mg/kg, IP) and additional blood samples were collected 1, 2 and 4 hours later. 2-DG, a glucose analogue, stimulates a centrally mediated activation of the adrenal medulla and to a lesser extent the postganglionic sympathetic neurons. For purposes of analysis, data were excluded from animals which died within 4 hours after injection. Basal plasma levels of both catecholamines were similar in adult and aged rats. Administration of 2-DG was attended by significant and sustained increases in plasma NE and EPI in rats of both ages. A greater proportion of aged rats died following administration of 2-DG compared to adult rats. At the higher dose of 2-DG, plasma levels of NE were significantly higher in 6 month old rats at 1 and 2 hours post-injection. In contrast, plasma levels of EPI were significantly higher in 24 month old rats at 1 and 2 hours after administration of 250 mg/kg 2-DG and at 1 hour after administration of 500 mg/kg 2-DG.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗

PubMed1984

Strain differences in sympathetic-adrenal medullary responsiveness and behavior.

Three experiments confirmed and extended previous findings from this laboratory regarding strain differences in physiological and behavioral responses of rats to stressful stimulation. In the first experiment, adult male Wistar-Kyoto (WKY) rats had greater plasma levels of norepinephrine and epinephrine and higher mean arterial pressures following 5 min of intermittent footshock (2.0 mA, 0.5-sec duration, every 6 sec) compared to adult male Brown-Norway (B-N) rats. In contrast, basal plasma levels of both catecholamines and resting values of mean arterial pressure and heart rate did not differ between strains when rats were undisturbed in their home cages. The second experiment involved a behavioral comparison of adult male and female WKY and B-N rats during 3 consecutive daily tests in an open field arena. B-N males and females were dramatically more active and reared more frequently during each open field test compared to WKY rats. For the third experiment, adult male and female rats of the two strains were trained in a one-trial passive avoidance task and median crossover latencies were similar for all strain-sex comparisons. However, median 24-hr retention latencies were much greater for WKY male and female rats. These findings indicate that strain differences in the physiological and behavioral responses of WKY and B-N rats are consistent across sexes. Moreover, our studies with these inbred strains of rats provide a convenient model for examining the relationship between sympathetic-adrenal medullary activity and behavioral responses to stressful stimulation.

Adrenal Medulla↗

PubMed1984

Dopamine may be a neurohormone in rat adrenal cortex.

In the periphery, dopamine (DA) is a precursor for norepinephrine (NE) and epinephrine (EPI) biosynthesis and is itself a neurotransmitter in sympathetic ganglia. In addition, DA may function as a neurohormone in providing maximum tonic inhibition of aldosterone secretion from the adrenal cortex. We have quantified the catecholamine content of the adrenal gland and have examined factors that regulate DA content of the adrenal cortex. Adult male Sprague-Dawley rats were assigned to one of four groups: adrenal demedullated (ADM); adrenal denervated via splanchnic nerve section (ADN); adrenal demedullated-denervated (DMN); and sham-operated controls (Sham). Ten days after surgery, rats were killed by decapitation, and the adrenals were removed and later assayed for catecholamine content. Compared with Sham, ADM and DMN decreased NE and EPI levels by 92-99% but DA levels by only 57-58%. ADN decreased levels of each catecholamine by 18-26%. These findings indicate that the adrenal cortex contains approximately 40% of the total gland content of DA and less than 8% of the total gland content of NE and EPI. Furthermore, DA in the adrenal cortex does not appear to require an intact splanchnic nerve supply to the adrenal. In a second experiment, we examined the effects of inhibition of catecholamine biosynthesis with alpha-methyl-p-tyrosine (alpha-MPT) on DA content in Sham and ADM rats. In Sham rats, alpha-MPT decreased adrenal DA by 44% and heart NE by 37%. In contrast, treatment of ADM rats with alpha-MPT increased adrenal DA by 49% but decreased heart NE by 36%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗

PubMed1984

Cardiovascular and sympathetic-adrenal medullary responses of rats to shock-induced aggression.

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Adrenal Medulla↗

PubMed1983

Plasma catecholamines in fasted and sucrose supplemented rats.

Rats were food deprived or given a sucrose supplemented diet for 3 days. Resting plasma catecholamine levels measured remotely from undisturbed rats were not altered by either dietary treatment. However, food deprivation did result in decreases in resting mean arterial blood pressure, heart rate, plasma volume and plasma Na+ concentration. After one minute of intermittent footshock food deprived and sucrose fed rats did not differ from controls with respect to blood pressure, heart rate or plasma catecholamine levels but food deprived rats were less active during footshock and had lower levels of plasma glucose immediately after footshock when compared to controls or sucrose fed rats. Food deprivation and dietary sucrose supplementation have been shown to alter norepinephrine (NE) turnover in specific sympathetic target tissues. Our data indicate that these changes in turnover are not reflected by changes in plasma NE. Therefore, NE turnover rates and plasma NE concentration may not be equivalent indices of sympathetic activity.

Adrenal Medulla↗

PubMed1983

Choline administration: lack of effect on plasma catecholamines in rats.

Choline chloride (35 or 70 mg/kg, IP) or saline was administered daily for 3 consecutive days to adult male Sprague-Dawley rats. Before and 30, 60 and 120 minutes after the third injection of choline chloride or saline, blood samples were collected from a chronic tail artery catheter and later analyzed for levels of norepinephrine (NE) and epinephrine (EPI). Plasma levels of both catecholamines did not differ between choline- and saline-injected rats at either of the four sampling points. When insulin (10 IU/kg, SC) was administered to stimulate the sympathetic-adrenal medullary system reflexly, plasma levels of NE and EPI increased significantly above basal values but were similar for choline- and saline-injected rats. These findings do not support a role for choline availability in the regulation of catecholamine secretion from the adrenal medulla.

Animals↗

PubMed1983

Adaptation to stress: tyrosine hydroxylase activity and catecholamine release.

The effects of adaptation to stress and of genetic differences on levels of in vitro tyrosine hydroxylase (TH) activity and in vivo catecholamine (CA) release are reviewed. It is shown that adaptation of animals to a wide variety of stressors including immobilization, electroconvulsive shock, footshock, hemorrhage, exercise and cold exposure results in a reduced CA response in the plasma, brainstem and heart to subsequent exposure to the same stress. Adaptation to many of the latter stressors also produces increased in vitro levels of TH activity. A similar inverse relation between in vitro TH activity and in vivo CA release is described for two inbred rat strains which differ in emotionality (Brown-Norway and Wistar Kyoto). The inverse relationship between TH activity and CA release may reflect different processes of biochemical adaptation utilized either for acclimation to stress, for preparation for emergency reactions or for changes in the metabolic costs of transmitter release. The similarity between environmental and genetic effects on these variables suggests that the above changes have a common adaptive function.

Adaptation, Psychological↗