Biomedical subjects

R McCarty

Publications and source records attributed to R McCarty.

At least 37 records · Page 2Linked to original sources

PubMed1995

Age-related changes in plasma catecholamine and glucose responses of F-344 rats to a single footshock as used in inhibitory avoidance training.

Young adult (3 months) and aged (22 months) Fischer 344 male rats were prepared with chronic tail artery catheters. Two days after surgery, rats were transferred to a test chamber and exposed to a single footshock (0, 0.25, 0.50, or 1.0 mA for 1 s). Blood samples were obtained from each rat under basal conditions and at timed intervals after exposure to footshock. Basal plasma levels of norepinephrine (NE) and epinephrine (EPI) were similar for 3- and 22-month-old rats. In contrast, plasma glucose (GLU) levels were significantly lower in aged rats compared to young adults. Increments in plasma levels of EPI were greater in aged rats compared to young adult controls following transfer of rats to the test chamber. In addition, aged rats had potentiated plasma EPI responses to footshock. Finally, aged rats had greater plasma levels of both catecholamines up to 5 min after a single training footshock compared to young adult controls. However, the increased responsiveness of EPI in aged rats was not accompanied by proportionate increases in plasma GLU levels, i.e., the EPI-GLU relationship was uncoupled in aged rats. These findings point to dramatic differences between young adult and aged rats in their plasma EPI responses to inhibitory avoidance training. Age-related increases in EPI secreted from the adrenal medulla, together with decreased blood GLU responses, may contribute in part to age-related deficits in memory modulatory processes.

Aging↗

PubMed1995

Milk electrolyte content of Dahl hypertensive and normotensive rats.

Milk samples were collected from lightly anesthetized lactating female rats of the Dahl hypertension-sensitive (SS/Jr) and Dahl hypertension-resistent (SR/Jr) inbred strains on postnatal days 8, 14 and 18. These milk samples were stored at 4 degrees C until analyzed for content of calcium (Ca++), magnesium (Mg++), chloride (Cl-), potassium (K+), sodium (Na+), and total protein. Our findings revealed that milk samples from females of the two strains were remarkably similar in content of electrolytes and total protein at each of the three sampling times. The only significant difference from among a total of 18 strain comparisons across the three sample times was that milk levels of Ca++ were significantly higher in SS/Jrs compared to SR/Jrs on postnatal day 14. These findings clearly indicate that these milk constituents do not differ between mothers of the two Dahl strains. Thus, milk concentrations of electrolytes and protein do not appear to serve as an environmental stimulus during the preweanling period for the dramatic age-related increases in arterial pressure characteristic of the SS/Jr strain.

Animals↗

PubMed1995

Age-related changes in plasma catecholamine responses to chronic intermittent stress.

We examined habituation and sensitization of plasma catecholamine responses to stressful stimulation in young adult (3 months) and aged (22 months) Fischer 344 (F-344) male rats. Aged rats had greater elevations in plasma levels of norepinephrine (NE) and epinephrine (EPI) following exposure to restraint stress compared to young adult controls. Within ages, plasma catecholamine responses were similar in rats stressed for the first time compared to those stressed for the 27th time. When chronically stressed young adult and aged F-344 rats were exposed to a novel stressor, swim stress at 25 degrees C, plasma catecholamine responses were significantly greater than for age-matched handled controls. The magnitude of sensitization of plasma catecholamine responses to the novel stressor was similar for young adult and aged F-344 rats. These results indicate that aged rats have enhanced plasma catecholamine responses to acute restraint stress compared to young adults. In addition, rats of both ages displayed comparable levels of sensitization of plasma catecholamine responses to a novel stressor. These findings emphasize that aged rats differ from young adult rats in some but not all aspects of sympathetic-adrenal medullary regulation. Further, these age-related differences in sympathetic-adrenal medullary responses are unmasked when animals are exposed to stressful stimulation.

Adrenal Medulla↗

PubMed1995

Effects of exposure to stressors of varying predictability on adrenal function in rats.

For 5 days, rats were exposed to shocks that were signalled by a light 0, 33, 66, or 100% of the time. Basal hormone levels and responses to a light-shock pair were measured daily. Greater predictability was associated with higher basal plasma corticosterone and norepinephrine levels indicative of chronic stress. Habituation of the corticosterone response was also less in the groups with greater predictability. However, predictability did not affect plasma prolactin or epinephrine responses. Because the endocrine systems responded differently, it is unlikely that the changes were due to a unitary process. Greater predictability appeared to be more stressful in this paradigm. Both associative and nonassociative factors have major roles in determining the hormonal responses to repeated presentation of stressors.

Adrenal Glands↗

PubMed1995

Baroreflex control of heart rate in Dahl hypertensive (SS/Jr) and normotensive (SR/Jr) rats.

OBJECTIVE: To determine whether impaired reflex control of heart rate was evident in rats of the inbred Dahl hypertension-sensitive (SS/Jr) strains. DESIGN AND METHODS: Phenylephrine and sodium nitroprusside were administered through jugular catheters in graded doses to elicit a range of pressor and depressor responses, for which corresponding reflex decreases and increases in heart rate were recorded. To assess the relative contributions of sympathetic and parasympathetic branches of autonomic control to baroreflex functioning, atropine methyl nitrate and atenolol were administered to establish vagal blockade, and cardiac sympathetic blockade, respectively. RESULTS: Assuming a sigmoidal relationship between mean arterial pressure and heart rate changes, our results indicated that SS/Jr rats exhibited elevated blood pressure set-points for baroreceptor activation and roughly similar baroreflex sensitivity compared with SR/Jr rats. In contrast, using linear regression analyses, our results indicated that SS/Jr rats had significant reductions in baroreceptor sensitivity when arterial pressure was increased by phenylephrine. Baroreceptor sensitivity was similar between rats of the two strains when arterial pressure was reduced by administration of nitroprusside. Atropine and atenolol had similar effects on baroreflex control of heart rate in both strains. However, pressor responses to phenylephrine were significantly greater in SS/Jr rats, an effect which had previously been reported in Dahl salt-sensitive (DS) rats and attributed to deficits in autonomic reflex control of vascular resistance. CONCLUSION: The present results indicate that the method of analysis for determination of baroreceptor sensitivity can influence the conclusions drawn in studies of hypertensive and normotensive strains of rat. Although deficits in baroreflex control of heart rate have consistently been reported in DS rats, the present results did not confirm those findings in inbred Dahl rats when mean arterial pressure and heart rate change data were analyzed by fitting a logistic equation to sigmoid data. In contrast, using linear regression analysis, those same data did reveal a defect in baroreceptor sensitivity of SS/Jr rats after acute increases in arterial pressure. Caution should be exercised in the selection of a method for analysis of baroreceptor data and the interpretation of the findings.

Animals↗

PubMed1995

Development of hypertension in spontaneously hypertensive rats: role of milk electrolytes.

1. Milk samples were collected from lactating spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) normotensive females at 8, 14 or 18 days postpartum. 2. Milk samples were later analysed for content of calcium (Ca++), sodium (Na+), potassium (K+), chloride (Cl-) and total protein. 3. Milk samples from SHR females had significantly higher concentrations of Na+ (at 8 and 14 days) and Cl- and significantly lower concentrations of Ca++, K+ (at 8 and 14 days) and total protein compared to milk samples from WKY females. 4. Preweanling dietary content of several electrolytes implicated in the development of hypertension differed dramatically between SHR and WKY strains. This altered diet early in life may serve as an environmental trigger for progressive age-related increases in arterial pressure in SHR.

Animals↗

PubMed1995

Decreased central and peripheral catecholaminergic activation in obese Zucker rats.

The Zucker rat is an animal model of autosomal recessive obesity characterized by excessive hypothalamic-pituitary-adrenal (HPA) axis and parasympathetic activities and deficient sympathetic outflow. Alterations in norepinephrine (NE) release, reuptake, and metabolism in the hypothalamic paraventricular nucleus (PVN) could also contribute to dysregulation of the HPA axis in obese Zucker rats via effects on corticotropin-releasing hormone neurons or could be secondary to some other primary defect. The present study assessed whether the obese phenotype defect. The present study assessed whether the obese phenotype (fa/fa) compared to the lean phenotype (Fa/?) of this strain was also associated with alterations in basal and immobilization (IMMO) stress-induced noradrenergic activation in the PVN, using in vivo microdialysis. To evaluate concurrent activity of the peripheral sympathetic nervous system and the HPA axis, we also measured plasma concentrations of catecholamines, ACTH, and corticosterone. IMMO-induced increases in PVN NE levels were significantly lower in obese Zucker rats, as were elevations in plasma concentrations of dihydroxyphenylglycol and epinephrine. Basal and IMMO-stimulated plasma ACTH concentrations were similar in obese and lean rats. Basal plasma corticosterone concentrations were also similar in obese and lean rats; however, IMMO-stimulated corticosterone levels were significantly greater in obese than in lean animals. Basal plasma free corticosterone levels, measured by ultrafiltration, were significantly higher in obese than in lean rats, confirming the state of chronic hypercorticosteronism in these animals. These findings indicate that obese Zucker rats have diminished central noradrenergic and peripheral sympathetic nervous system responses to IMMO stress along with a chronically hyperactive HPA axis. We suggest that defective regulation of PVN NE reflects and contributes to the development and/or maintenance of obesity in Zucker rats via central hypoactivity of the sympathetic system. The hypercorticosteronism of these animals, apparently sustained by some nonadrenergic stimulatory input, might participate in the suppression of the sympathetic system.

Adrenocorticotropic Hormone↗

PubMed1994

Timing of preweanling maternal effects on development of hypertension in SHR rats.

Cross-fostering of litters was used to determine the timing of preweanling maternal influences on the development of high blood pressure in spontaneously hypertensive (SHR) rats. The SHR litters were either reared by their natural mothers or reciprocally cross-fostered to normotensive Wistar-Kyoto (WKY) mothers for postnatal days 1-7, 1-14, 1-21, 8-21, or 15-21. All SHR litters were weaned at 21 days of age and males were housed in groups of two to three per cage until physiological measures were obtained at 100 days of age. At 100 days of age, all rats were surgically prepared with tail artery catheters and, on the day after surgery, direct measures of mean arterial pressure (MAP, mmHg) and heart rate (HR, bpm) were obtained while rats were resting and undisturbed in their individual home cages. Our findings indicate that cross-fostering SHR pups to WKY foster mothers was attended by significant effects on body weights at weaning and on adult MAPs. Compared to control SHRs, cross-fostered SHRs, with the exception of the 15-21-day group, were significantly heavier at weaning. By 100 days of age, body weights of SHRs were similar across treatment groups. Basal MAPs of SHRs cross-fostered for days 1-7, 1-14, 1-21, and 8-21, but not days 15-21, were reduced significantly compared to SHR controls reared by their natural mothers. In contrast, basal HRs were not affected in any of the cross-fostered SHR groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Maternal influences on milk intake in SHR and WKY pups.

Mother to pup milk transfer was examined in the spontaneously hypertensive rat (SHR) and its normotensive progenitor, the Wistar-Kyoto (WKY). Litters of SHR and WKY pups were either reared by their natural mothers or cross-fostered to mothers of the opposite strain shortly after birth. At postpartum days 7 and 14, pup body weights were monitored throughout a 2-h maternal separation period followed by a 3-h refeeding period during which pups remained with their mothers. Weight increases of pups over the refeeding period served as an indirect measure of milk ingestion. At postpartum day 7, both SHR and WKY pups nursed by SHR mothers received lower quantities of milk compared to their counterparts nursed by WKY mothers. Maternal strain differences in milk transfer were largely attenuated at postpartum day 14. The different nutritional environments provided by SHR and WKY mothers may mediate the alterations in offspring cardiovascular physiology and physical development that occur with reciprocal cross-fostering.

Animals↗

PubMed1993

Altered gustatory development in Na(+)-restricted rats is not explained by low Na+ levels in mothers' milk.

Placing pregnant rats on a sodium-deficient diet (0.03% NaCl) very early in gestation and then weaning the offspring (sodium-restricted rats) to the same diet precludes development of amiloride-sensitive sodium taste transduction pathways in the offspring. However, normal amiloride-sensitive sodium taste responses can be restored by permitting sodium ingestion by sodium-restricted rats. The present study tested the hypothesis that the concentration of sodium in sodium-restricted mothers' milk must be abnormally low in order to preserve altered gustatory function in the offspring. Other milk electrolyte and total protein concentrations were determined as well. Milk sodium was similar between sodium-restricted and control rat mothers at 10-13 and 16-20 days postpartum, as were levels of potassium and chloride. At 10-13 days postpartum, total protein was higher in milk from sodium-restricted mothers. Sodium-restricted mothers' milk calcium concentrations were higher versus controls at 16-20 days postpartum. These results indicate that the lack of gustatory amiloride sensitivity in sodium-restricted rats cannot be attributed to deficient dietary sodium levels during the suckling period.

Amiloride↗

PubMed1992

Maternal involvement in the development of cardiovascular phenotype.

Over the past 20 years, laboratory studies of genetically defined animal models of human essential hypertension have provided valuable information on the pathophysiology of this disturbance in cardiovascular regulation. Relatively fewer studies have examined the impact of preweaning factors on the developing cardiovascular system of hypertensive animals. In our laboratory studies, we have utilized two inbred genetically hypertensive models: the spontaneously hypertensive (SHR) rat and its Wistar/Kyoto (WKY) normotensive control strain as well as the Dahl hypertension-sensitive (SS/Jr) and hypertension-resistant (SR/Jr) strains. To manipulate the preweaning maternal environment, we have employed the technique of reciprocal cross-fostering of litters between hypertensive and matched normotensive mothers. Our findings to date point to the maternal environment as a powerful influence on the development of high blood pressure in genetically hypertensive rats. In general, hypertensive rats reared by normotensive foster mothers have significant reductions in arterial blood pressure in adulthood. Thus, the progression of hypertensive disease is not strictly predetermined by genotypic factors. Rather, a genetic predisposition to hypertension interacts with preweaning environmental factors to determine an animal's cardiovascular phenotype in adulthood.

Animals↗

PubMed1992

Shared maternal influences in the development of high blood pressure in the spontaneously hypertensive (SHR) and Dahl salt-sensitive (SS/Jr) rat strains.

The influence of maternal environment on the development of high blood pressure in spontaneously hypertensive (SHR) and Dahl salt-sensitive (SS/Jr) rats was examined using the technique of reciprocal cross-fostering. Previous experiments from this laboratory demonstrated that adult blood pressures of the SHR and SS/Jr strains were significantly attenuated when hypertensive-strain pups were fostered to a dam of the respective normotensive control strain during the preweaning period. In this study, SHR and SS/Jr pups were assigned to either a cross-fostered (fostered to a dam of the opposite hypertensive strain) or control-reared condition within 24 h of birth. Adult resting blood pressures were similar in control and cross-fostered SHR rats and in control and cross-fostered SS/Jr rats. Heart rates and heart, adrenal, and kidney weights were also similar in control and cross-fostered rats of each strain. However, body weights of SHR rats reared by an SS/Jr dam were somewhat lower compared to control-reared SHR rats. These data indicate that the maternal environments provided by SHR and SS/Jr mothers are similar in some way such that they permit the development and full expression of the hypertensive phenotype in both same-strain and opposite-strain pups.

Animals↗

PubMed1991

Plasma catecholamine responses to acute motion stress in laboratory rats.

Plasma levels of norepinephrine (NE) and epinephrine (EPI) were measured in adult male Fischer 344 (F-344) laboratory rats exposed to acute motion stress. Two days prior to testing, rats were prepared with chronic tail artery catheters to permit remote sampling of blood from conscious, freely behaving animals. Animals remained in their home cages during the entire testing protocol. After collection of basal blood samples, cages were rotated at 45 revolutions per minute for a 10-minute period each hour for 5 consecutive hours. Additional blood samples were collected immediately after each of the 10-minute rotation stress sessions. Plasma levels of NE remained unchanged from baseline immediately following each of the rotation stress sessions. In contrast, plasma EPI increased significantly above baseline levels following each of the 5 rotation stress sessions. These data indicate that rotation stress provides a selective activation of epinephrine-containing adrenal chromaffin cells as reflected in an increase in plasma EPI but not NE. This stress model could prove valuable in examining the physiological and behavioral consequences of adrenal EPI release in freely behaving animals without the confounding effects of increases in circulating norepinephrine.

Adrenal Medulla↗

PubMed1991

Adult blood pressure reduction in spontaneously hypertensive rats reared by normotensive Sprague-Dawley mothers.

Spontaneously hypertensive (SHR), Wistar-Kyoto (WKY) normotensive, and Sprague-Dawley (SD) normotensive rats were either reared by their natural mothers (controls) or fostered to a mother of one of the other strains. The effects of rearing environment were assessed by measures of body weight at weaning and adult resting mean arterial blood pressure (MAP) and heart rate (HR). At weaning, SHR control rats weighed less than WKY controls which in turn weighed less than SD controls. SHR and WKY rats reared by SD mothers weighed significantly more than their respective controls, whereas SD rats reared by either SHR or WKY mothers weighed less than SD control rats. Manipulation of the maternal environment was attended by a change in adult resting MAP in only one group. SHR rats reared by SD mothers had MAPs which were significantly lower than SHRs reared by their natural mothers. No within-strain adult HR differences were observed between control and cross-fostered groups. These data indicate that the effects of cross-fostering on adult resting MAP previously reported for SHR and WKY animals are generalizable to another normotensive strain. That is, genetically hypertensive (SHR) animals exposed to a normotensive (WKY or SD) maternal environment display a reduction in adult resting MAP, whereas hypertension or an increase in adult MAP is not induced in normotensive rats (WKY or SD) as a consequence of exposure to a hypertensive maternal environment.

Animals↗

PubMed1991

Two new Wistar-Kyoto rat strains in which hypertension and hyperactivity are expressed separately.

Two inbred strains have been developed from a cross between SHR and WKY. WK-HTs are hypertensive but not hyperactive, and WK-HAs are hyperactive but normotensive. Together with SHR (that express both traits) and WKY (expressing neither trait) we used four strains to follow correlations of biological changes with the expression of hyperactivity or hypertension. We show that the well known sympathetic hyperreactivity of SHRs to acute stress is associated with the hyperactivity trait and not the hypertension among the four strains. Similarly, the well known ventricular hypertrophy in SHRs is more prominent among the hyperactive strains than the hypertensives. Examination of regional brain amine levels revealed an imbalance in forebrain serotonin transmission in the hyperactive strains, and no significant correlations with hypertension. On the other hand, neuropeptides in brainstem and spinal cord revealed a decrease, in hypertension, in neuropeptide Y and PNMT content of terminals of C1 fibers that innervate the spinal cord sympathetic outflow. Also, the two hypertensive strains showed increased TRH-and proctolin-like immunoreactivity in fibers that innervate the C1 cells in the rostral ventrolateral medulla. These findings illustrate the unique advantage provided by WK-HA and WK-HT strains as additional controls for SHRs in studying hypertension and hyperactivity.

Adrenal Medulla↗

PubMed1990

Habituation and sensitization of plasma catecholamine responses to chronic intermittent stress: effects of stressor intensity.

Adult male Sprague-Dawley rats were exposed acutely (1 time for 30 minutes) or chronically (30 minutes per day for 27 days) to swim stress in water maintained at either 18 degrees C, 24 degrees C or 34 degrees C. Each rat was prepared with an indwelling tail artery catheter to allow for direct measures of mean arterial pressure (MAP, mmHg) and heart rate (HR, beats per minute) and for remote collection of blood samples before, during and after the 1st or 27th swim stress session. Blood samples were later analyzed for plasma levels of norepinephrine and epinephrine to serve as an assessment of sympathetic-adrenal medullary activity. Compared to handled controls, body weight gain was reduced significantly in rats exposed chronically to swim stress at any of the 3 temperatures. However, baseline values of MAP and HR and plasma levels of norepinephrine and epinephrine were similar in chronically stressed rats compared to their handled controls. The plasma norepinephrine response of rats exposed chronically to either 18 degrees C or 24 degrees C swim stress was significantly greater than that of matched controls stressed for the first time. In contrast, the plasma epinephrine response of chronically stressed rats from these two groups was slightly but not significantly reduced compared to matched controls. For swim stress at 34 degrees C, the plasma norepinephrine and epinephrine responses of chronically stressed rats were reduced significantly compared to controls stressed for the first time. These findings demonstrate that stressor intensity affects sensitization and habituation of plasma catecholamine responses in laboratory rats exposed to chronic intermittent stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Glycemic control of pain threshold in diabetic and control rats.

Pain threshold was assessed via tail flick latency in alloxan-diabetic, streptozotocin-diabetic, BB/W-diabetic, and control laboratory rats. In addition, tail flick latency was determined under conditions of both euglycemia (60-120 mg/dl) and hyperglycemia (greater than 250 mg/dl). Conditions of hyperglycemia resulted in a significant decrease in tail flick latency in both diabetic and control animals. More interestingly, tail flick latency was returned to control values in diabetic rats following normalization of blood glucose levels. It is concluded that elevated blood glucose levels result in a decrease in pain threshold in both diabetic and control rats. In addition, a permanent state of painful symptoms may be avoided in clinical diabetes by improvement of diabetic control.

Animals↗

PubMed1990

Predictability of chronic intermittent stress: effects on sympathetic-adrenal medullary responses of laboratory rats.

This experiment involved an examination of sympathetic-adrenal medullary responses of laboratory rats following exposure to chronic intermittent stress. Animals were assigned at random to one of three groups: (i) controls, handled briefly each day; (ii) restraint stress (RS), restrained for 30 min per day; or (iii) variable stress (VS), exposure to restraint, cold swim, or intermittent footshock during one of five time periods each day. On the 26th day, rats were prepared with chronic tail artery catheters for remote sampling of blood and direct measurement of mean arterial pressure and heart rate. On Day 28, rats of each group were exposed to 30 min of restraint stress and timed blood samples were collected and later analyzed for content of norepinephrine (NE) and epinephrine (EPI). VS rats gained significantly less body weight compared to control and RS rats. Basal measures of blood pressure and heart rate and of plasma NE and EPI were comparable for rats of the three groups. The plasma catecholamine responses to restraint stress on Day 28 were significantly reduced in RS and VS rats compared to first-time stressed controls. These findings suggest that predictability of the type of stressor and the time of its occurrence does not influence the pattern of diminished sympathetic-adrenal medullary responses of animals exposed to chronic intermittent stress.

Adrenal Medulla↗