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Biomedical subjects

R McCarty

Publications and source records attributed to R McCarty.

At least 37 records · Page 2Linked to original sources

Maternal influences on sympathetic-adrenal medullary system in spontaneously hypertensive rats.

The technique of reciprocal cross fostering was used to assess the influence of the maternal environment on the functioning of the sympathetic-adrenal medullary system in the spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) normotensive rats. Control, in-fostered, and cross-fostered rats were tested in adulthood to assess 1) the neural contribution to resting mean arterial blood pressure (MAP) and 2) sympathetic-adrenal medullary responses to acute footshock stress. Adult resting MAP was significantly lower in cross-fostered SHRs (139.6 mmHg) compared with control or in-fostered SHRs (162.1 and 159.3 mmHg). In addition, the decrease in MAP after sympathetic blockade (40.6 mmHg) was significantly less in cross-fostered SHRs compared with controls (50.1 mmHg). Sympathetic-adrenal medullary responses to foot-shock were greater in SHR than WKY rats; however, cross-fostered SHRs showed exaggerated responses compared with control and in-fostered SHRs. Altering the maternal environment did not produce any measurable effects on the neural contribution to resting MAP or sympathetic-adrenal medullary responsivity to acute stress in the WKY strain. These results indicate that the blood pressure-lowering effect of cross fostering in the SHR strain is caused in part by a dampening of the neural contribution to resting MAP; however, these animals retain their strain's characteristic adrenergic hyperreactivity to stressful stimulation.

Adrenal Medulla

Physiological responses to acute stress in alloxan and streptozotocin diabetic rats.

Physiological responses to acute stress were assessed in alloxan diabetic, streptozotocin diabetic and control laboratory rats. Rats were prepared with indwelling tail artery catheters to allow for direct measurement of mean arterial pressure (MAP, mmHg) and heart rate (HR, beats per minute) and remote sampling of blood. Within 24 hours after surgery, basal values of MAP and HR were determined. Two days after surgery, rats were subjected to 5 minutes of intermittent footshock. Blood samples were collected before footshock stress and immediately and 15 minutes after termination of footshock. Plasma levels of norepinephrine (NE) and epinephrine (EPI) increased significantly above basal values in all animals exposed to acute footshock stress. However, in approximately one-half of alloxan and streptozotocin diabetic rats, plasma levels of EPI under basal conditions and following footshock stress were elevated significantly compared to controls and the remaining diabetic animals. We have denoted these subgroups of diabetic animals as reactive responders (plasma EPI greater than controls) and nonreactive responders (plasma EPI similar to controls), respectively. Plasma levels of NE under basal conditions and following footshock stress were similar in reactive responders and nonreactive responders compared to matched controls. Baseline blood glucose levels were elevated in alloxan and streptozotocin diabetic rats compared to controls. Blood glucose levels increased reliably in all animals following footshock stress. Basal MAPs were reduced significantly in both subgroups of alloxan and streptozotocin diabetic rats compared to matched controls. In contrast, resting HRs were similar between diabetic rats and their corresponding controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Alloxan

Habituation of sympathetic-adrenal medullary responses following exposure to chronic intermittent stress.

Two experiments examined sympathetic-adrenal medullary responses of laboratory rats after exposure to a brief period of stressful stimulation daily for 26 consecutive days. In the first experiment, rats were exposed to restraint stress for 30 minutes per day and in the second experiment, rats were exposed to inescapable footshock for 10 minutes per day. For each experiment, handled controls were stressed acutely to provide a basis for comparison with chronically stressed animals. In both experiments, chronically stressed rats gained less weight than controls. Basal plasma levels of norepinephrine (NE) and epinephrine (EPI) were similar in control and chronically stressed rats. However, there was a substantial attenuation of the plasma catecholamine response to the 27th episode of restraint or footshock compared to acutely stressed controls. These findings indicate that sympathetic-adrenal medullary responses are dampened considerably in animals exposed to a highly predictable regimen of chronic intermittent stress.

Adrenal Medulla

Sympathetic-adrenal medullary responses to acute stress in Dahl hypertensive (S/JR) rats.

Sympathetic-adrenal medullary responses to acute footshock stress were assessed in inbred Dahl salt-sensitive (S/JR) and salt-resistant (R/JR) rats by measuring plasma levels of norepinephrine (NE) and epinephrine (EPI). Ten-week-old S/JR and R/JR rats were surgically prepared with indwelling tail artery catheters which permitted direct measurements of mean arterial pressure (MAP, mmHg) and heart rate (HR, beats/min) and remote sampling of blood. Two days after surgery, S/JR and R/JR rats were subjected to an acute stress paradigm. Blood samples were collected before and 3 minutes after transfer of rats to a shock chamber, after 1 minute of intermittent footshock, and again 5 minutes later. S/JR rats had significantly higher resting MAP's compared to R/JR rats. In contrast, baseline heart rates were similar for rats of the two strains. Basal plasma levels of NE and EPI were also similar in S/JR and R/JR rats. Upon transfer from the home cage to a shock chamber, S/JR rats exhibited significant increases in plasma levels of both catecholamines, while R/JR rats maintained circulating levels of NE and EPI that were near baseline values. However, S/JR and R/JR rats had similar increments in plasma NE and EPI following acute footshock stress. Five minutes after footshock, levels of NE and EPI returned toward baseline values for R/JR's, but remained significantly elevated above baseline in hypertensive S/JR rats. These data suggest that S/JR rats are more responsive than R/JR controls to the mild stress of transfer, but exhibit comparable responses to the more intense stress of inescapable footshock.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla

Sensitization of sympathetic-adrenal medullary responses to a novel stressor in chronically stressed laboratory rats.

Studies from this and other laboratories have demonstrated that sympathetic-adrenal medullary responses are reduced in laboratory rats exposed to chronic intermittent stress. To extend these findings, we have conducted three experiments in which laboratory rats were exposed daily for 26 consecutive days to the same (homotypic) stressor and then challenged with a novel (heterotypic) stressor. Each stress session lasted for 30 minutes and the following homotypic/heterotypic treatments were included: Experiment 1--restraint/footshock; Experiment 2--cold swim/restraint; and Experiment 3--footshock/cold swim. Controls were exposed to the heterotypic stressor only. Plasma levels of norepinephrine (NE) and epinephrine (EPI) were measured in blood samples taken from control and chronically stressed rats to provide an assessment of sympathetic-adrenal medullary activity. In each experiment, chronically stressed rats gained significantly less weight than handled controls. Basal plasma levels of NE and EPI were similar for chronically stressed and control rats. In contrast, plasma catecholamine responses to the heterotypic stressor were significantly greater in stressed rats compared to controls that were stressed for the first time. This pattern of exaggerated responses was especially evident for the cold swim/restraint and footshock/cold swim groups. These findings provide evidence for a sensitization of sympathetic-adrenal medullary responses to a novel stressor in animals previously exposed to chronic intermittent stress.

Adrenal Medulla

Cardiovascular and sympathetic nervous system responses to an acute stressor in borderline hypertensive rats (BHR).

The present study examined cardiovascular and plasma catecholamine responses to acute footshock stress in adult male Wistar-Kyoto (WKY) normotensive, borderline hypertensive (BHR), and spontaneously hypertensive (SHR) rats. Basal mean arterial pressure and heart rate were equivalent for SHRs and BHRs, and levels for both groups were elevated compared to WKYs. Following transfer to the footshock chamber, blood pressure increased to a greater degree in SHRs than in WKYs or BHRs. However, the tachycardia was exaggerated in both BHRs and SHRs compared to WKYs. In response to intermittent footshock stress, all groups had comparable heart rate increases while maintaining blood pressure near baseline levels. SHRs demonstrated a sympathetic hyperresponsiveness to footshock stress, with greater increases in plasma norepinephrine and epinephrine levels than WKYs immediately following footshock. At 5 minutes postfootshock, plasma catecholamines remained elevated in SHRs over both WKYs and BHRs. Plasma catecholamine increases following footshock were comparable at all time points between WKYs and BHRs. The present results demonstrate that sympathetic responsiveness of BHRs to acute footshock stress is more similar to normotensive WKYs than to hypertensive SHRs.

Animals

Open-field behavior of spontaneously hypertensive and Wistar-Kyoto normotensive rats: effects of reciprocal cross-fostering.

The influence of the maternal environment on the development of open-field behavior in spontaneously hypertensive (SHR) rats was investigated using the technique of reciprocal cross-fostering. Entire litters of SHR and Wistar-Kyoto (WKY) normotensive rats were either reared by their natural mothers, in-fostered to dams of the same strain, or cross-fostered to dams of the opposite strain on the day after birth. Open-field behavior was assessed in male and female rats from the six groups (2 strains x 3 rearing conditions) at 30, 60, 90, and 120 days of age. Animals were observed in the open-field during a 5-min test period and the number of squares entered and hindlimb rears were recorded. At all ages tested, SHR rats were more active in the open field, entering more squares and rearing more frequently than WKYs. SHR females were more active than age-matched SHR males, while no sex differences were apparent in the WKY strain. At each age, open-field behavior was similar across WKY rearing groups. SHR control and in-fostered animals responded similarly in the open field; however, SHR cross-fostered rats (particularly females) tended to be more active than controls. Although cross-fostering has profound effects on cardiovascular development and functioning in the SHR, it appears that altering the early maternal environment experienced by SHR pups does not grossly affect the development of open-field behavior.

Animals

Central oxytocin systems may mediate a cardiovascular response to acute stress in rats.

The role of central nervous system arginine vasopressin (AVP) and oxytocin (OXY) in the cardiovascular response to acute stress was examined using three experimental models: pharmacological antagonism of central AVP-OXY receptors; lesions of the paraventricular nucleus (PVN); and rats genetically lacking in AVP synthesis, i.e., the Brattleboro strain. Central administration of an AVP-OXY antagonist abolished the increase in heart rate (HR) seen following acute footshock stress. The group receiving centrally administered antagonist increased HR 15 +/- 17 (SE) beats/min, whereas, in contrast, the group receiving intravenous administration of the antagonist showed a 66 +/- 17 beats/min increase, and the group receiving intraventricular antagonist vehicle showed a 101 +/- 14 beats/min increase in response to stress. In a second study, electrolytic lesions of the PVN also blocked the increase in HR seen following stress, 20 +/- 12 beats/min for PVN-lesioned rats, 74 +/- 25 beats/min for sham lesion rats, and 93 +/- 7 beats/min for rats with a lesion not destroying the PVN. In the final study, the responses of Brattleboro rats, i.e., rats genetically deficient in vasopressin synthesis, were equivalent to their Long-Evans controls (131 +/- 13 and 147 +/- 12 beats/min, respectively). In each of these studies, the blood pressure responses to the stressor were equivalent for control and experimental groups. The results of these studies suggest that a neuropeptide system originating in or passing through the PVN may play an important role in the cardiovascular responses to stress and further suggest that the central OXY system may be one pathway mediating this response.

Acute Disease

Maternal environment and development of high blood pressure in Dahl hypertensive rats.

The contribution of the preweanling maternal environment to the development of hypertension was examined using the technique of reciprocal cross-fostering between two inbred rat strains, the Dahl hypertension-sensitive (SS/Jr) rat and the Dahl hypertension-resistant (SR/Jr) rat. Litters of SS/Jr and SR/Jr pups were reared by their natural mother, in-fostered to a dam of the same strain, or cross-fostered to a dam of the opposite strain for the entire preweanling period from postnatal days 1 to 30. At 60 and 100 days of age, one rat from each litter was surgically prepared with an indwelling catheter in the ventral tail artery. One day after surgery, measures of resting mean arterial pressure and heart rate were taken as the animals were resting and undisturbed in their home cages. Body weights were also obtained at 30, 60, and 100 days of age as a measure of general somatic development. Our findings indicate that SS/Jr rats fostered to SR/Jr dams exhibited a significant reduction in resting mean arterial pressure compared with naturally reared or in-fostered SS/Jr rats (P less than 0.01 at 60 days and P less than 0.03 at 100 days). Conversely, arterial pressure of SR/Jr rats did not differ across rearing conditions at either age. Body weights were not significantly affected by cross-fostering in either strain. We conclude from these results that characteristics of the SS/Jr maternal environment interact with the inbred genetic susceptibility of the SS/Jr pup to elicit the full expression of the SS/Jr hypertensive phenotype.

Animals

Differential plasma catecholamine and neuropeptide Y responses to acute stress in rats.

Neuropeptide Y (NPY) is a vasoconstrictor present in the sympatho-adrenomedullary system and may be co-released with norepinephrine (NE) and epinephrine (EPI) during sympathetic activation. We studied plasma NPY-immunoreactivity (-ir, radioimmunoassay) and catecholamine (radioenzymatic) responses during two acute stress paradigms that differ in character, intensity, and duration. The intermittent stress of footshock (0.75 and 1.5 mA, 0.5 sec duration, at 5-sec intervals, for 5 min) evoked intensity-dependent immediate increments in plasma NE and EPI, and a delayed NPY-ir response (+0.6 +/- 0.1 pmol/ml). Prolonged (60 min) immobilization caused greater increases in plasma NE and EPI levels and no changes in plasma NPY-ir until the end of the stress session (+0.3 +/- 0.1 pmol/ml). Plasma NPY-ir responses correlated with those of NE but not with EPI suggesting a sympathetic origin for the release of the peptide. Relatively greater NPY-ir responses to footshock than to immobilization may be consistent with a preferential release of the peptide by a bursting but not continuous mode of sympathetic activation. However, it may also be due to a differential activation of the sympathetic nerves and adrenal medulla by these two stress situations.

Animals

Effect of stressor intensity on habituation of the adrenocortical stress response.

Although it is known that the number of presentations of a stressor can influence the adrenocortical stress response, relatively little information exists on how stressor intensity affects this process. To evaluate this, we repeatedly presented rats with stressors of 3 different intensities and sampled blood for corticosterone. The first major finding was that the rat's initial adrenocortical responsiveness regardless of the stressor employed was a critical variable. Rats that showed a small corticosterone response showed no evidence of habituation or of differences due to stressor intensity. Rats that showed an initial robust response all showed partial habituation of their corticosterone response over time but the patterns varied with stressor intensity. Handled and prone restrained rats showed the same pattern but rats subjected to the more intense stressor of supine restraint showed delay in habituation and tonically elevated responses. These data indicate that individual differences in reactivity to stressors as well as stressor intensity can influence the pattern of the stress response over the course of repeated administration of the stressor.

Adrenal Cortex

Sympathetic-adrenal medullary response to stress in hyperactive and hypertensive rats.

Sympathetic-adrenal medullary hyperreactivity to acute stress, measured as an exaggerated elevation of plasma epinephrine and norepinephrine levels in response to footshock, was examined in four genetically related, inbred rat strains, all derived from the Wistar-Kyoto rat (WKY). These four strains are endowed with the traits of hypertension and behavioral hyperactivity, expressed either together (in SHR), or separately in two new strains (Wistar-Kyoto hyperactive rats, WK-HA, and Wistar-Kyoto hypertensive rats, WK-HT), or not at all (in WKY). Male rats of the SHR, WKY, WK-HA and WK-HT strains were subjected to acute footshock stress in order to determine whether the previously reported hyperreactivity of the SHR is attributable to the hypertensive trait, or to the behavioral hyperactivity trait, both of which are characteristic of the SHR. Plasma catecholamine levels were determined prior to, immediately following, and 5 min following acute footshock stress. We report here that the WK-HA strain (hyperactive but not hypertensive) exhibited the hyperreactivity characteristic of SHRs, and not the WK-HT strain (hypertensive but not hyperactive). We conclude that the exaggerated sympathetic-adrenal medullary response to acute stress is associated with the hyperactivity trait and not with hypertension among these congenic rat strains.

Adrenal Medulla

Regulation of binding sites for atrial natriuretic factor (ANF) in rat brain.

In two experiments, binding sites for atrial natriuretic factor (ANF) were studied in discrete areas of rat brain by quantitative autoradiography. In the first experiment, the maximum binding capacity of 125I-ANF was reduced significantly in the subfornical organ and choroid plexus of 4 and 14 week old spontaneously hypertensive (SHR) rats compared to aged-matched Wistar-Kyoto (WKY) normotensive controls. In contrast, the maximum binding capacity of 125I-ANF in the area postrema was similar for young and adult SHR and WKY rats. The second experiment involved a comparison of brain ANF binding sites in Long-Evans control rats and Brattleboro rats with inherited diabetes insipidus. The maximum binding capacity of 125I-ANF was significantly greater in the subfornical organ of Brattleboro rats compared to Long-Evans controls. However, no strain differences occurred for 125I-ANF binding in the choroid plexus or area postrema. These findings indicate that the number of ANF binding sites in discrete areas of rat brain may be influenced in a highly selective fashion by alterations in body fluid homeostasis (i.e., hypertension or diabetes insipidus). Changes in brain ANF binding sites within circumventricular areas may involve central as well as peripheral sources of ANF-related peptides.

Aging

Chronic stress and sympathetic-adrenal medullary responsiveness.

Acute exposure of animals to stressful stimulation is attended by a significant activation of the sympathetic-adrenal medullary system. If animals are exposed to the same stressful stimulus each day for several weeks, a number of adaptive changes occur in the sympathetic-adrenal medullary system, including increased synthesis and storage of catecholamines, increased basal levels of circulating catecholamines, and decreased release of catecholamines into the circulation following exposure to the identical (homotypic) stressful stimulus. If chronically stressed animals are exposed to a novel (heterotypic) stressful stimulus, there is an exaggerated response of the sympathetic-adrenal medullary system compared to animals exposed to the same stressful stimulus for the first time. Other neuroendocrine systems share some characteristics with the sympathetic-adrenal medullary system in its pattern of adaptation to chronic stress. Several variables appear to influence this pattern of neuroendocrine adaptation to stressful stimulation, including predictability of the stressor, the intensity and duration of the stressor, the interval between each episode of stress, and the number of presentations of the stressor. The pattern of neuroendocrine adaptation to chronic intermittent stressful stimulation resembles in some respects the processes of habituation and sensitization.

Adrenal Medulla

Brain binding sites for atrial natriuretic factor (ANF): alterations in prehypertensive Dahl salt-sensitive (S/JR) rats.

The binding of radioiodinated atrial natriuretic factor (125I-ANF-28) to discrete areas of brain in 7 week old, inbred Dahl salt-sensitive (S/JR) and salt-resistant (R/JR) rats was studied utilizing quantitative film autoradiography. At this age, S/JR rats exhibit systolic blood pressures that are prehypertensive and tend to be slightly higher than systolic blood pressures of age-matched R/JR rats. Scatchard analysis of 125I-ANF-28 binding in forebrain revealed that S/JR rats have a significantly increased number of binding sites for 125I-ANF-28 in the subfornical organ as compared to R/JR controls. In contrast, values for 125I-ANF-28 binding capacity in the choroid plexus and area postrema were similar for both strains, and binding affinity constants for 125I-ANF-28 binding revealed no strain differences in any brain area examined. The elevation in the number of binding sites for atrial natriuretic factor may serve as a compensatory mechanism acting in part to lower fluid volume and sodium levels prior to the precipitous increase in blood pressure which occurs in S/JR rats by 10 weeks of age.

Animals

ANF receptors: distribution and regulation in central and peripheral tissues.

Atrial natriuretic factor is a recently-discovered family of biologically active peptides produced in, stored and secreted by mammalian atria. ANF exerts a wide variety of actions in the periphery as well as within the central nervous system. In general, these actions are directed toward the maintenance of body fluid and electrolyte balance and regulation of arterial blood pressure. In a fashion similar to that of many other hormonal systems, the actions of ANF in various target tissues appear to be mediated by at least one class of specific receptors. However, while the biosynthesis and biological actions of ANF have been extensively investigated, little research has been focused on ANF receptor systems. In this article, we will provide an overview of current literature regarding the distribution and binding characteristics of receptor sites for ANF in peripheral and central target tissues. In addition, we will consider factors involved in the regulation and alteration of ANF receptor sites in various tissues. Finally, a brief discussion of the emerging concept of ANF and angiotensin II as mutual antagonists in body fluid homeostasis and cardiovascular regulation will be offered.

Animals

Maternal effects on the development of spontaneous hypertension.

Cross-fostering spontaneously hypertensive rat (SHR) pups to Wistar-Kyoto (WKY) normotensive mothers influenced physical development, resting mean arterial pressure and heart rate, open-field behavior, and sympathetic-adrenal medullary responses to stressors. In contrast, cross-fostering WKY pups to SHR mothers at birth did not affect these developmental processes.

Animals