Robert E. Stewart

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.

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.

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)

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.

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.

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.

Binding sites for atrial natriuretic factor (ANF) in kidneys and adrenal glands of spontaneously hypertensive (SHR) rats

Binding sites for atrial natriuretic factor (ANF) were studied in kidneys and adrenal glands of 17 week old male spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) normotensive rats by quantitative autoradiography using 125I-ANF-28. In kidney, 125I-ANF-28 binding sites were found in high concentrations in glomeruli and in much lower concentrations in the renal papilla. In adrenal gland, 125I-ANF-28 binding sites were highly localized to the zona glomerulosa and were of moderate density in the inner cortical regions. ANF binding sites did not occur in the adrenal medulla. The maximum binding capacity (Bmax) of 125I-ANF-28 was reduced by 50% in the kidney glomeruli of SHRs compared to WKY controls. In contrast, the affinity constant (Ka) for 125I-ANF-28 was elevated by 100% in kidney glomeruli of SHRs. There were no significant strain differences in values for Bmax or Ka for 125I-ANF-28 binding in the adrenal zona glomerulosa. These findings suggest that the natriuretic and diuretic actions of ANF within kidney glomeruli may be compromised in adult SHR rats and these alterations may contribute to the development and maintenance of hypertension in rats of this strain.

Habituation of plasma catecholamine responses to chronic intermittent restraint stress

Adult male Sprague-Dawley rats were exposed to restraint stress (RS) for 30 min per day for 0, 5, 12, or 26 consecutive days. Each animal was then surgically prepared with an indwelling tail-artery catheter to permit direct measurements of mean arterial pressure (MAP, in mm Hg) and heart rate (HR, in beats per minute) on the day after surgery, and remote collection of blood samples during RS 2 days after surgery. Blood samples were later analyzed for plasma levels of norepinephrine and epinephrine to provide an assessment of the activity of the sympathetic-adrenal medullary system. Body-weight gain was reduced significantly in rats stressed for 12 or 26 days relative to handled controls. Baseline values of HR and of plasma levels of norepinephrine and epinephrine were similar in animals of the four groups. Baseline MAPs were lower in control rats and in those stressed for 26 days than in rats stressed for the previous 5 or 12 days. Plasma catecholamine responses to RS were reduced significantly in animals during the 6th, 13th, or 27th stress session relative to subjects restrained for the first time. These findings indicate that sympathetic-adrenal medullary responses are dampened rapidly when laboratory rats are exposed to chronic intermittent RS. In addition, the results of this experiment are consistent with our suggestion that habituation of sympathetic-adrenal medullary responsiveness occurs in animals exposed to chronic intermittent stress.

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.

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.