Chronic effects of high salt intake and conflict stress on blood pressure in primates. A progress report.

The effects of combined behavioral stress and high dietary salt on blood pressure were examined in baboons (N = 4) over the course of 1 year. Either high salt diet (240 mEq Na+/day) or conflict stress were administered for 8 to 16 weeks, followed by high salt intake and stress combined. Mean arterial pressure (MAP) increased by 8 mmHg during high dietary salt alone, by 4 mmHg during stress alone, and increased further to 14 mmHg above baseline during combined salt and stress. Control baboons (N = 2) had no change in MAP across 47 weeks. The data indicate additive effects of chronic high dietary salt intake and behavioral stress on blood pressure in non-human primates.     

Biobehavioral effects of extended salt loading and conflict stress in intact baboons.

Behavioral stressors may inhibit sodium excretion, potentially increasing plasma volume and elevating blood pressure during chronic exposure. Blood pressure regulation may be especially deranged during manipulations that further challenge the kidney, such as a diet high in salt content. The effects on blood pressure and other variables of combined behavioral stress (food/shock conflict) and dietary salt (12 g NaCl per day; 218 mEq Na+ per day) were examined in adult male baboons over the course of 1 year. Mean arterial pressure was not significantly elevated over baseline after 5 months of high dietary salt alone (6 +/- 5 mmHg) but was maximally elevated by an average of 17 (+/- 3 SEM) mmHg after 5 months of combined salt and conflict stress. Control baboons showed no significant trends in mean arterial pressure across the same time period. Individual subjects whose blood pressure was "salt+stress resistant" or "salt+stress sensitive" were differentiated by their degree of pressure diuresis and natriuresis, urinary free cortisol, and a behavioral index of stress sensitivity. The data indicate additive effects of chronic high dietary salt intake and behavioral stressors on blood pressure in nonhuman primates that are dependent on renal function and pituitary-adrenocortical activity.     

Blood pressure hyperreactivity in non-human primates during dietary sodium combined with behavioral stress

The potential for behavioral stress alone or combined with dietary salt to augment pressor reactivity to the onset of daily experimental sessions was examined in normotensive, intact baboons over the course of four months. During twice daily experimental sessions, adult male baboons experienced food/shock conflict such that lever pulling not only served to earn food, but was also occasionally punished with cued mild electric shock. Blood pressure and heart rate were measured during a baseline period of fixed-ratio food reinforcement (3 weeks), during conflict stress (2 weeks), and after dietary salt was added to the daily conflict protocol (CONFLICT + SODIUM, 3 weeks). Reactivity, i.e., acute changes in blood pressure and heart rate to the daily experimental sessions, was not evident during food reinforcement sessions nor during the CONFLICT stress alone condition. The addition of a high salt diet virtually doubled blood pressure increases and heart rate decreases to the onset of experimental sessions. Average reactivities during CONFLICT + SODIUM periods were 11.2/7.9% delta for SBP/DBP (systolic/diastolic blood pressure, mmHg), and -5.65% delta for HR (heart rate, BPM). Neither atenolol nor hydrochlorothiazide diuretic significantly altered cardiovascular reactivity during CONFLICT + SODIUM in comparison to a preceding non-drug CONFLICT + SODIUM period. When atenolol and diuretic effects were directly compared, atenolol mildly augmented, while diuretic mildly decreased DBP but not SBP reactivity during CONFLICT + SODIUM. Reactivity was eliminated after salt loading and behavioral sessions were terminated. These findings provide evidence that enhanced salt ingestion may synergistically act with behavioral stress to produce pressor hyperresponsiveness to otherwise benign environmental events.     

Potassium supplementation induces beneficial cardiovascular changes during rest and stress in salt sensitive individuals.

The typical American diet includes high salt and low potassium, a pattern linked to elevated blood pressure (BP) in cross-cultural studies. This study compared resting and stress cardiovascular responses on a high salt, low potassium diet to those observed during 2 interventions: salt restriction and potassium supplementation. Forty-seven percent of the primarily normotensive sample (n = 67 adults) were salt sensitive, showing a decrease in mean arterial pressure > or = 5 mmHg during low salt and equivalent reductions during high potassium. The equivalent benefits of the interventions were maintained, but not enhanced, during exposure to behavioral stress (i.e., no effect on reactivity). Salt resistants (SRs) exhibited no change in resting or stress BP across the diets. High salt increased cardiac index in both groups, whereas vascular tone was decreased only in the SR group. High potassium produced hemodynamic benefits similar to low salt, even with continued high salt intake.     

Open-field behavior in two models of genetic hypertension and the behavioral effects of salt excess

In order to assess the relationship of behavior to blood pressure and salt intake, open-field behavior was studied in 123 rats of the spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), Sprague-Dawley (SD), and Dahl resistant (DR) and sensitive (DS) strains. DS rats become hypertensive upon exposure to either high dietary salt or psychogenic stress, while DR rats remain normotensive. A circular photobeam open field was used under full room illumination. Three 5-min trials were given on consecutive days. Rats were tested with or without 5 days of an 8% NaCl diet. We found that DS rats were less active than DR rats, regardless of diet. In contrast, SHR rats were more active than WKY rats. However, DS and SHR rats were equally active. Thus, behavioral differences between these two models of hypertension are expressed by the normotensive control strains. The relative ranking of activity levels between strains was DR = SD greater than SHR = DS greater than WKY. High-salt-enhanced intertrial habituation, defined as the decrease in activity across trials (DS, 100%; SD, 82%; SHR, 90%; WKY, 1350%; but DR, -50%) as well as intratrial habituation, defined as the decrease from the first to the second half of the trial (14%, all subjects). Defecation was increased with high salt (DS, 975%; SD, 59%; SHR, 267%; WKY, 89%; but DR, 40%). These effects of high salt may reflect an increase in an emotionality factor. DR rats were largely resistant to the behavioral effects of salt. Total activity was positively correlated with blood pressure in hypertensive rats, r(42) = 0.33, p less than .01, but negatively correlated in normotensive rats, r(81) = -0.34, p less than .01. The proportion of total activity occurring in the first half of the trial for the initial test day was correlated with blood pressure in normotensive rats r(81) = 0.44, p less than .01. Dietary salt excess has behavioral as well as cardiovascular consequences.     

Effects of a high salt diet on blood pressure responses to acoustic stimuli in borderline hypertensive rats (BHR)

The borderline hypertensive rat (BHR) responds to environmental and dietary stressors with elevated blood pressure. The first two months of a high salt diet appear to be the time of greatest sensitivity to salt effects on the blood pressure of BHR. The current study was conducted to examine whether exposure to salt diets varying in duration for up to two months differentially affects baseline blood pressures (systolic, SBP, and diastolic, DBP) and blood pressure responses to novel acoustic stimuli in BHR and normotensive Wistar-Kyoto (WKY) rats. Male BHR and WKY were fed a control (1%) salt diet or a high (8%) salt diet for 1, 1.5, 2.5, or 8.5 weeks. SBP and DBP responses to an acoustic stimulus (85 dB, 3 kHz) were measured upon completion of the diets at 12 weeks of age. Ten acoustic trials (one stimulus/minute) were presented and blood pressure responses were recorded in 2-second blocks spanning the 10 seconds prior to and following stimulus presentation. BHR had higher resting SBP and DBP than WKY, and 8.5 weeks of 8 percent salt increased SBP markedly in BHR. SBP and DBP labilities in the initial trial were greater in BHR than WKY with high salt diet durations of 2.5 and 8.5 weeks producing greater lability in later trials. Few differences were noted in pressor responses, but BHR had more dramatic depressor responses than WKY in early trials, and BHR pressures had a more dramatic return to baseline. It appears that genetic history and salt diet can affect blood pressure lability and recovery in response to novel stimuli in genetically susceptible animals.     

Behavioral performance effects of verapamil in normotensive and renovascular hypertensive baboons.

Behavioral performances of normotensive and hypertensive adult male baboons were tested before, during, and following chronic oral dosing with verapamil. Performances during a five-color simultaneous match-to-sample task were measured for two doses (2.0, and 3.2 mg/kg/day) and vehicle. Each dose was administered for 21 consecutive days preceded and followed by 14-day baseline and recovery periods, respectively. Choice reaction times increased by 9% during the lower dose of verapamil, compared to vehicle; choice reaction times were unchanged at the higher dose. At baseline and during vehicle administration, the yellow and white stimuli were the most difficult to discriminate correctly; discrimination of these colors was slightly impaired by the lower, but not the higher dose of verapamil. Verapamil's behavioral effects were not modulated by blood pressure changes since both baboon groups showed equivalent changes in behavioral performance, but only renovascular hypertensive baboons showed blood pressure decreases. Verapamil appears to be an effective hypotensive and does not produce profound psychomotor impairment at clinically used doses during the first weeks of treatment.     

Behavioral performance effects of verapamil in normotensive and renovascular hypertensive baboons

Behavioral performances of normotensive and hypertensive adult male baboons were tested before, during, and following chronic oral dosing with verapamil. Performances during a five-color simultaneous match-to-sample task were measured for two doses (2.0, and 3.2 mg/kg/day) and vehicle. Each dose was administered for 21 consecutive days preceded and followed by 14-day baseline and recovery periods, respectively. Choice reaction times increased by 9% during the lower dose of verapamil, compared to vehicle; choice reaction times were unchanged at the higher dose. At baseline and during vehicle administration, the yellow and white stimuli were the most difficult to discriminate correctly; discrimination of these colors was slightly impaired by the lower, but not the higher dose of verapamil. Verapamil’s behavioral effects were not modulated by blood pressure changes since both baboon groups showed equivalent changes in behavioral performance, but only renovascular hypertensive baboons showed blood pressure decreases. Verapamil appears to be an effective hypotensive and does not produce profound psychomotor impairment at clinically used doses during the first weeks of treatment.     

Effects of social defeat on acute cardiovascular response in salt-sensitive and salt-resistant rats

We studied the effects of social stress (SS) and a high salt diet on systolic blood pressure (SBP) and heart rate (HR): S/JR male rats (which exhibit marked elevations in SBP when placed on a high sodium diet) and R/JR male rats (which are resistant to the BP-elevating effects of a high sodium diet) were maintained on a low sodium diet (0.3% NaCl) or placed on a high sodium diet (8% NaCl). Within each dietary condition independent groups were either exposed to SS, by placement in the cage of a trained fighter male (Long-Evans breed) for 25 min, or exposed to no stress. The dietary regimen was imposed for 10 days with stress exposures on Days 1, 2, 3, 5, 7, and 9, with SBP and HR measured indirectly by tail plethysmography 3 min following exposure to SS. SS produced an acute decrease in SBP (20-30 mm Hg) in S/JR rats on the second and subsequent exposures, but did not affect HR. SS did not affect SBP of R/JR rats, but did produce a significant elevation of HR. Maintenance on the high sodium diet increased SBP in S/JR, but not R/JR, rats when it was measured on the eighth (no stress) day, but SS obscured the effects of diet on SBP on days when rats were stressed. Following exposure to attacks, defeated SS rats displayed an upright submissive posture relatively late during the first stress exposure when no change in SBP was observed after SS in S/JRs, but displayed the submissive posture immediately and with long duration on the second and subsequent exposures when a marked decrement in SBP was seen.     

Lipid reactivity to stress: II. Biological and behavioral influences.

This study examined behavioral and physiological influences on lipid concentrations during acute and chronic stressors. One hundred men (n = 92) and women (n = 8) were tested during a chronic stressor and during 2 acute stressors. During chronic stress, diet, physical activity, exercise, and sleep were examined. During the acute stressors, catecholamines, cortisol, plasma volume, and cardiovascular responses were examined. None of the behavioral influences could explain the lipid response to chronic stress. Responses of the atherogenic lipids to acute stressors were not solely reflecting hemoconcentration of the plasma but were moderately correlated with cardiovascular, epinephrine, and cortisol reactivity. Diastolic blood pressure reactors to the acute stressors had larger lipid responses to the chronic stressor than did nonreactors. Elevations in blood lipids during stress are not artifacts and may be clinically significant.     

Caffeine enhances the physiological response to occupational stress in medical students

Caffeine (3.3 mg/kg) was tested against a placebo in 20 male medical students during periods of low (no exams) versus high (final exams) work stress. On each of 8 test days, heart rate and blood pressure were measured at baseline and over a 40-min postdrug interval; immediately afterward, blood was drawn to test plasma cortisol and serum lipid concentrations. Exams increased heart rate (p less than .005) and systolic blood pressure (p less than .02). Caffeine decreased heart rate (p less than .0001) and increased systolic blood pressure (p less than .005), diastolic blood pressure (p less than .0001), plasma cortisol levels (p less than .01), and serum cholesterol levels (p less than .02). Caffeine effects were additive with those of exams, and together they increased the number of men showing systolic blood pressures in the borderline hypertensive range. Thus, caffeine use during periods of increased occupational stress may enhance the cumulative stress response.     

High Versus Low Aggressive Priming During Video‐Game Training: Effects on Violent Action During Game Play,Hostility, Heart Rate,and Blood Pressure1

Playing violent video games is related to increased negative affect and cardiovascular reactivity. We examined the influence of high and low aggressive priming during video‐game training on violence during game play (e.g., shooting, choking), hostility, frustration with game play, blood pressure, and heart rate. Male undergraduates (N= 36) were assigned to a high aggressive or low aggressive video‐game priming condition. After training, they played Metal Gear Solid^(tm), which allows players to advance by using stealth, violence, or both. Participants in the high aggressive priming condition used significantly more violent action during game play and reported more hostility than those in the low aggressive priming condition. Heart rate was correlated with feelings of hostility. These findings indicate that both aggressive priming and use of game violence influence arousal and negative affect and might increase behavioral aggression.     

Food and amphetamine self-administration by baboons: effects of alternatives.

The effects of the availability of an alternative reinforcer on responding maintained by food pellets or fluid solutions were examined in 6 adult male baboons (Papio cynocephalus anubis). During daily 23-hr experimental sessions, baboons had concurrent access to both food pellets and fluid, with responding maintained under fixed-ratio schedules of reinforcement that varied between the two commodities. The fixed-ratio requirement, or cost, for pellets was increased when (a) no fluid, (b) a dilute dextrose vehicle, (c) 0.002 mg/kg d-amphetamine, or (d) 0.004 mg/kg d-amphetamine was available. When given nonrestricted concurrent access to food pellets and amphetamine at minimal cost (FR 2), baboons self-administered sufficient amphetamine to decrease pellet intake. Increasing the response requirement for pellets decreased pellet intake at a similar rate regardless of the available fluid and increased fluid intake in a variable manner among baboons such that there were no statistically significant increases in fluid intake. In contrast, when access to pellets was restricted to 70% of maximal intake under nonrestricted conditions, increasing pellet cost decreased pellet intake and increased fluid intake more rapidly when the high amphetamine dose was available. Thus, amphetamine was more effective as an economic substitute for pellets when access to pellets was restricted. The response cost for vehicle and both amphetamine concentrations was increased when baboons had nonrestricted and restricted access to pellets. Increasing the response requirement for fluid delivery decreased intake of all three fluids similarly under both pellet-access conditions. The results indicate that substitution between commodities with minimal commonalities can be studied under controlled laboratory conditions and is dependent upon reinforcement schedule and commodity restrictions.     

Personal Control in Chronic Pain Sufferers During Acute Interpersonal Stress

Among individuals with Rheumatoid Arthritis (RA), pain-associated stress can severely impact wellbeing. Psychological attributes, such as a sense of personal mastery, may attenuate the effects of chronic pain on life quality. We tested the hypothesis that a high sense of mastery would predict lower pain, perceived stress, fatigue, and mean arterial pressure (MAP) than would a low sense of mastery during an acute, interpersonal stressor.Seventy-four individuals with RA completed a psychophysiological laboratory session involving MAP measurements, as well as self-ratings of stress, joint pain, and fatigue. Measurements were collected before, during, and after an interpersonal stressor. To assess personal mastery, exploratory and confirmatory factor analyses were conducted on the Pearlin Mastery Scale based on recommendations by Reich and Zautra (1991)The Pearlin Mastery Scale yielded two distinct factors: fatalism and control. Both fatalism and control were significant predictors of the wellbeing variables. Individuals with a highly fatalistic style demonstrated higher general levels of mean arterial pressure (F(1) = 3.41, p<.1) and reported greater joint pain (F(1) = 4.72, p<.05) across all periods. Individuals with a high sense of control also evidenced lower MAP (F(1) = 3.73, p<.1) and reported less stress (F(1) = 7.44, p<.01) and fatigue (F(1) = 5.16, p<.05). Neither fatalism nor control were related to objective measures of disease severity (r's = -.10, p=NS and -.02, p=NS, respectively).RA patients with a high level of personal mastery, as evidenced by scores on two distinct indices, experience lower MAP, and report less pain, stress and fatigue. Although fatalism and control were not related to objective disease state, they seem to play an important role in the experience of wellbeing for people with RA.     

The paraventricular nucleus of the hypothalamus is involved in cardiovascular responses to acute restraint stress in rats

The paraventricular nucleus of the hypothalamus (PVN) has been implicated in several aspects of cardiovascular control. Stimulation of the PVN evokes changes in blood pressure and heart rate. Additionally, this brain area is connected to several limbic structures implicated in behavioral control, as well as to forebrain and brainstem structures involved in cardiovascular control. This evidence indicates that the PVN may modulate cardiovascular correlates of behavioral responses to stressful stimuli. Acute restraint is an unavoidable stressor that evokes marked and sustained cardiovascular changes, which are characterized by elevated mean arterial pressure (MAP) and an intense heart rate (HR) increase. We report on the effect of inhibition of PVN synapses on MAP and HR responses evoked by acute restraint in rats. Bilateral microinjection of the nonspecific synaptic blocker cobalt (CoCl(2), 1 mM/100 nl) into the PVN did not change the HR response or the initial peak of the MAP response to restraint stress, but reduced the area under the curve of the MAP response. Moreover, bilateral microinjection of cobalt in areas surrounding the PVN did not change the cardiovascular response to restraint. These results indicate that synapses in the PVN are involved in the neural pathway that controls blood pressure changes evoked by restraint.     

Food and cocaine self-administration by baboons: effects of alternatives.

The effects of the availability of an alternative reinforcer on responding maintained by food pellets or drug solutions were examined in 8 adult male baboons (Papio hamadrayas anubis). During daily 23-hr experimental sessions, baboons had access to both food pellets and fluid under a two-choice procedure, in which the response requirement, under a fixed-ratio schedule, differed for the two commodities. There were no restrictions on access to water, which was continuously available from a spout at the rear of each cage. In Experiment 1, the fixed-ratio requirement, or cost, for fluid delivery remained constant while the fixed-ratio requirement for pellets was changed every 2 or 3 days when (a) no fluid, (b) a dilute dextrose vehicle, (c) 0.008 mg/kg per delivery cocaine, (d) 0.016 mg/kg per delivery cocaine, or (e) 0.032 mg/kg per delivery cocaine was available concurrently. In Experiment 1, progressively increasing the response requirement for pellets decreased pellet intake, but for 4 baboons pellet intake at maximum pellet cost was lower when cocaine, compared to the vehicle, was available. Increasing the response requirement for pellets had variable effects on vehicle intake. However, increasing the response requirement for pellets increased intake of at least one dose of cocaine to a greater extent than vehicle in all 8 baboons. Thus, cocaine could be considered a more effective economic substitute than vehicle for pellets. Experiment 2 systematically varied the order in which the response requirements for a pellet delivery were presented and added a control condition in which cocaine doses, yoked to the amount self-administered, were given three times during the session by the experimenter. Again, pellet intake at maximal pellet cost was lower when cocaine, compared to the vehicle, was available. In contrast, experimenter-given cocaine doses did not alter responding maintained by pellets. Thus, the effects of self-administered cocaine on responding maintained by food pellets differed from the effects of experimenter-given cocaine on responding maintained by food pellets.     

Cardiovascular reactivity and central adiposity in older African Americans.

This study examined central adiposity, as measured by waist circumference (WC), in relation to mental-stress induced systolic (SBP) and diastolic blood pressure (DBP) and heart rate (HR) responses, body composition, the metabolic syndrome, and health practices in 22 older, African American men and women (ages 52-79 years). The high WC (> 100 cm) group showed significantly greater SBP, DBP, and HR reactivity, greater fasting insulin levels, lower high density lipoprotein cholesterol levels, greater fat mass in both truncal and peripheral regions, and greater body mass index as compared to the low WC (< 100 cm) group. Groups were comparable with respect to fat-free mass, peak oxygen consumption (VO2), leisure time activity, dietary intake, resting blood pressure, and other metabolic variables. The findings support a clustering of metabolic and mental stress risk factors that may predispose older African Americans to increased cardiovascular and metabolic disease.     

Cardiovascular reactivity, mood, and task performance in deprived and nondeprived coffee drinkers

Forty habitual, heavy coffee drinkers (M = 5.7 cups/day) participated in two experimental sessions. Participants were deprived of their morning coffee for one of the laboratory sessions, not deprived the other. During each session, subjects consumed 12 oz of caffeinated coffee, decaffeinated coffee, or caffeine-free herbal tea. Measurements of heart rate, blood pressure, mood, and catecholamine response to deprivation and consumption of the beverage, alone and in combination with challenging tasks, were made. This study found that caffeine continues to cause blood pressure increases with chronic, heavy consumption and that these effects do not appear to habituate with regular use. Subjects reacted to behavioral challenge with fewer negative mood effects if they had consumed caffeine or coffee. Mild caffeine deprivation was associated with symptoms of stress.     

Stress and dietary practices in adolescents.

Baseline data from the Health and Behavior in Teenagers Study (HABITS) were used to investigate associations between stress and dietary practices in a socioeconomically and ethnically diverse sample of 4,320 schoolchildren (mean age = 11.83 years). Male (n = 2,578) and female (n = 1,742) pupils completed questionnaire measures of stress and 4 aspects of dietary practice (fatty food intake, fruit and vegetable intake, snacking, and breakfast consumption) and also provided demographic and anthropometric data. Multivariate analyses revealed that greater stress was associated with more fatty food intake, less fruit and vegetable intake, more snacking, and a reduced likelihood of daily breakfast consumption. These effects were independent of individual (gender, weight) and social (socioeconomic status, ethnicity) factors. Stress may contribute to long-term disease risk by steering the diet in a more unhealthy direction.     

Personal mastery predicts pain,stress, fatigue,and blood pressure in adults with rheumatoid arthritis

Among individuals with rheumatoid arthritis (RA), stress-associated disease flare can severely impact well-being. Psychological factors such as personal mastery may buffer an individual from the negative effects of those flares. We tested the hypothesis that a high sense of personal mastery would prospectively predict stress reactivity. Measures of pain, perceived stress, fatigue, and mean arterial pressure (MAP) were collected before, during, and after two interpersonal stressors conducted on 73 individuals with RA. Factor analysis of the personal mastery scale yielded two independent factors: a 5-item “fatalism” component and a 2-item “control” component. Individuals with high fatalism scores reported overall greater joint pain at baseline and those scoring high on control exhibited lower MAP, and reported less stress and fatigue at baseline. After controlling for baseline differences, those high in control exhibited greater MAP increase during stress, and less drop in pain when compared to those low in control. These results suggest that individuals high in control may be more susceptible to the effects of acute stress; however, the overall beneficial aspects of high control outweigh the acute negative effects. Personal mastery may play a role in the experience of pain, stress, and fatigue for people with RA.