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Biomedical subjects

S B Manuck

Publications and source records attributed to S B Manuck.

At least 19 recordsLinked to original sources
PubMed1995

Effects of acute psychological stress on serum lipid levels, hemoconcentration, and blood viscosity.

BACKGROUND: While there is substantial evidence that psychological stress enhances risk for coronary artery disease, the mechanisms underlying such an influence remain unclear. We examined the effects of short-term psychological stress on serum lipid levels, hemoconcentration, fibrinogen level, and plasma viscosity. METHODS: Forty-four healthy young adults were randomly assigned to perform a distinctly frustrating cognitive task for 20 minutes (stress condition) or to rest quietly for the same period (control condition). RESULTS: Relative to controls, stressed subjects showed significant increases in blood pressure and heart rate; total, low-density, and high-density lipoprotein cholesterol levels; hematocrit; hemoglobin level; and total protein concentration. Stressed subjects also showed significant reductions in plasma volume and increased plasma viscosity and estimated whole-blood viscosity compared with controls. A similar trend in fibrinogen level was not statistically significant. Individual differences in blood pressure and heart rate response to stress correlated highly with changes in total cholesterol levels and hematocrit. CONCLUSIONS: Our investigation provides further evidence that exposure to short-term mental stress elicits hemoconcentration with associated increases in serum lipid concentrations, hemostatic factors, and blood viscosity.

Acute Disease↗
PubMed1995

Aggression and brain serotonergic responsivity: response to slides in male macaques.

The association between central serotonergic responsivity (measured by prolactin response to acute administration of fenfluramine hydrochloride) and aggressivity was examined in 40 adult male cynomolgus monkeys (Macaca fascicularis). Prolactin response to fenfluramine was distributed bimodally with 24 monkeys displaying a "low" prolactin response and 15 showing a "high" prolactin response to the fenfluramine challenge. Behavioral responsivity was assessed by placing the monkeys individually in an open-field enclosure and presenting a series of photographic slides depicting both threatening and nonthreatening images. Monkeys that were low prolactin responders displayed significantly more aggressive gestures in response to a threatening slide of a human being than did the high responders (p < 0.05). Insofar as fenfluramine-stimulated prolactin release assesses serotonergic responsivity, these data support related findings in people and nonhuman primates linking reduced serotonergic activity and aggression.

Aggression↗
PubMed1995

Beta 2-adrenergic receptor density and cardiovascular response to mental stress.

In this study we evaluated effects of an acute experimental stressor on beta 2-adrenoceptor density and examined the relationships of baseline receptor density to cardiovascular reactions induced by stress. In addition, we investigated whether any observed alterations in receptor density were associated with concomitant redistribution of circulating lymphocyte populations. Receptor density and lymphocyte subsets were determined before and immediately following performance of a frustrating laboratory task in 22 male volunteers. Blood pressure, heart rate (HR), and plasma catecholamine concentrations were also assessed at baseline and during task performance. Parallel measurements were obtained among 11 unstressed control subjects. Receptor density increased significantly between baseline and posttask measurements, but equally so in experimental and control subjects. Numbers of T suppressor/cytotoxic and natural killer cells increased selectively among subjects assigned to the experimental (stress) condition. However, there was no association between lymphocyte subset distribution and receptor density. Interindividual variability in pretask receptor density correlated significantly with heart rate and systolic blood pressure (SBP) reactivity during the initial 3 min of mental stress, but not over the entire task period. In addition, baseline receptor density correlated with SBP (but not HR) reactivity after covariance adjustment for the concomitant change in plasma catecholamine concentrations.

Adolescent↗
PubMed1995

Dominant social status and contraceptive hormone treatment inhibit atherogenesis in premenopausal monkeys.

The stress of social subordination is associated with exacerbation of coronary artery atherosclerosis in premenopausal cynomolgus monkeys, possibly as a result of the ovarian dysfunction that reliably accompanies subordinate social status. The primary objective of the current study was to determine whether treatment with an oral contraceptive (OC) provides relative protection from development of atherosclerotic plaques, especially among animals made vulnerable to atherosclerosis by social subordination. In the present study, 193 adult female monkeys (Macaca fascicularis) were placed in social groups of 5 or 6 animals each. Half of the animals were then fed an atherogenic diet to which had been added a triphasic OC, while the remainder received only the atherogenic diet. At the end of 26 months, atherosclerosis was measured in an iliac artery biopsy taken from each monkey. The results demonstrated that among untreated animals subordinate individuals developed significantly more atherosclerosis than did their dominant counterparts (P < .01); however, OC treatment inhibited atherosclerosis in subordinate animals (P < .05) and eliminated the difference between dominant and subordinate animals that was observed in the untreated condition. Subordinate social status and OC treatment were both associated with reduced plasma concentrations of HDL cholesterol (P < .01 for both), and subordinate monkeys also had elevations in LDL cholesterol plus VLDL cholesterol (P < .01). Nonetheless, the interaction between social status and OC treatment remained significant even after covariance adjustment for variation in plasma lipids. Taken together, these results suggest that social subordination worsens, whereas OC treatment inhibits, atherosclerosis, and that these effects are independent of concomitant variability in plasma lipids.

Animals↗
PubMed1994

Antiatherogenic effects of beta-adrenergic blocking agents: theoretical, experimental, and epidemiologic considerations.

Theoretical considerations and results from experimental studies in animal models suggest that long-term beta-adrenergic blockade should be antiatherogenic. Some of these experimental results indicate that beta-blockers could inhibit atherogenesis and thus prevent clinical events independently of any effects on blood pressure through concomitant reductions in heart rate, blood velocity and energy, endothelial permeability to lipoproteins, and the likelihood of plaque rupture. Any such independent inhibition of atherogenesis implies, in turn, that beta-blockers might be more desirable than alternative antihypertensive therapies in persons at high risk for atherosclerotic diseases. Results of the three major trials directly comparing beta-blockers to diuretics in the primary prevention of coronary heart disease among patients with hypertension were largely inconclusive. However, ancillary data from these and other trials are consistent in demonstrating that beta-adrenergic blockade is associated with anti-coronary heart disease effects and, thus, is perhaps antiatherogenic. A definitive evaluation of the antiatherogenic effects of beta-blockers is not forthcoming because no large clinical trials directly assessing the effect of these drugs on atherosclerosis have been done or are planned.

Adrenergic beta-Antagonists↗
PubMed1994

A multidimensional measurement model for cardiovascular reactivity: stability and cross-validation in two adult samples.

The factor structure for measures of stress-related cardiovascular reactivity was examined in 2 samples: a university campus employee sample (N = 72) and a sample of young adult twins (N = 113). In both samples, 5 noninvasive cardiovascular measures were monitored during a series of challenging laboratory tasks. We developed a 2-factor model depicting vascular and cardiac influences on responding. With confirmatory factor analysis, this model was shown to be consistent with the data across both samples, across 2 testing sessions, and across 2 sets of tasks. Latent variables measuring cardiac and vascular reactivity were highly reliable on retest as well. Individual differences in cardiovascular reactivity to mental stress may be characterized by a stable, 2-dimensional pattern of response.

Adolescent↗
PubMed1994

Dexamethasone resistance among nonhuman primates associated with a selective decrease of glucocorticoid receptors in the hippocampus and a history of social instability.

We have studied some of the neuroendocrine and social correlates of dexamethasone resistance in a nonhuman primate population. Subjects were 51 male Macaca fascicularis monkeys with known behavioral histories and who had been given dexamethasone (DEX) suppression tests a week prior to killing. We compared the subset of monkeys who were most DEX responsive (post-DEX cortisol values of 3.1 +/- 0.5 micrograms/dl) versus a DEX-resistant subset (cortisol values of 9.2 +/- 2.0 micrograms/dl); we found two features that distinguished these groups: (a) DEX-resistant monkeys had significantly fewer available glucocorticoid receptor (GR) binding sites in the hippocampus; they did not differ in numbers of mineralocorticoid receptor (MR) sites in the hippocampus, nor in numbers for either receptor in the cortex or hypothalamus as a whole. (b) Animals had resided for a number of years in social groups that were either stable or were repeatedly destabilized by changing of group membership; the latter has been shown to constitute a sustained stressor. DEX-resistant animals were more than twice as likely to have come from an unstable group as were DEX-responsive monkeys. Rodent studies have shown that sustained stress can cause a selective downregulatory decrease in the numbers of hippocampal corticosteroid receptors, and that such a loss is associated with DEX resistance. The present data suggest similar associations in the primate, and may be of relevance to the DEX resistance observed in a subset of human depressives.

Animals↗
PubMed1993

Low versus high prolactin responders to fenfluramine challenge: marker of behavioral differences in adult male cynomolgus macaques.

Prolactin response to acute administration of fenfluramine hydrochloride is considered an indirect assessment of "net" central serotonergic activity. This study compared behavioral characteristics of adult, male cynomolgus macaques (Macaca fascicularis) having "low" or "high" prolactin responses to fenfluramine challenge. The subjects were 75 animals housed in five-member social groups for 28 months. In month 23, prolactin responses to fenfluramine challenge were evaluated. Observations of specific behaviors (aggressive, submissive, affiliative, and nonsocial) were made three times per week on animals in each social group. The dominance status of each animal within a social group was assessed at weekly intervals. Low prolactin responders had a significantly higher index of "overt" aggression (ratio of fights involving physical contact and chasing or lunging/all forms of aggressive behavior) compared to high prolactin responders (p < .03). There were no differences in the dominance status of low and high responders (p = .34). Furthermore, low responders were more socially withdrawn than high responders, as they spent significantly more time alone (passive or neutral state; p < .03) and less time in passive body contact with other animals than high responders (p < .05). These data support the hypothesis that reduced central serotonergic activity in nonhuman primates is associated with a high level of overt aggression and a low level of positive social interaction.

Aggression↗
PubMed1993

Family history studies in hypertension research. Review of the literature.

Reviewed in the present article are over 150 family history studies of essential hypertension. By comparing normotensive individuals with and without a family history of hypertension, these investigations seek to identify potential pathophysiologic factors that predate the development of high blood pressure. The research literatures summarized here represent four general areas: 1) cellular salt transport mechanisms, 2) dietary sodium, intravascular volume, and renal function, 3) cardiovascular morphology and physiology, and 4) cardiovascular reactivity. There is strong evidence of early cardiac morphologic changes (greater left ventricular wall thickness and mass) and altered peripheral vascular capacity and responsivity to pressor stimuli among normotensive individuals with a positive family history. In contrast, cardiac output, sodium consumption, intravascular volume, and cardiovascular responses to isometric exercise and standing do not differ in persons with and without a family history of hypertension. Other articles are characterized by inconsistent results, which may be a reflection of the heterogeneity of essential hypertension, but also may be due to methodological weaknesses. The latter include failure to confirm the blood pressure status of ostensibly hypertensive or normotensive family members and the use of relatively weak study designs (eg, where a positive history is defined by a single, hypertensive first-degree relative).

Biological Transport↗
PubMed1993

Plaque changes and arterial enlargement in atherosclerotic monkeys after manipulation of diet and social environment.

To study the effects of dietary and social manipulations on lesion progression in male monkeys with established atherosclerosis, 83 animals fed a diet containing 1 mg cholesterol per kcal for 14 months were either necropsied (baseline group, n = 21) or assigned to one of three experimental conditions: 1) a diet containing a high amount of fat and cholesterol and a stressful social situation (HiFC-stress, n = 18); 2) a diet lower in fat and cholesterol and a stressful social situation (LoFC-stress, n = 21); or 3) the low-fat, low-cholesterol diet and a nonstressful social situation (LoFC-no stress, n = 23). After 28 months, all animals were necropsied. Coronary atherogenesis was arrested among monkeys in the LoFC-stress and LoFC-no stress conditions compared with that of animals in the baseline condition (plaque areas of 0.35 mm2, 0.30 mm2, and 0.38 mm2, respectively). Lesions in animals fed the LoFC diet (both stress and no-stress groups) were significantly smaller than those in monkeys in the HiFC-stress condition (0.96 mm2). Furthermore, aortic cholesterol content was significantly decreased and luminal areas were relatively larger among monkeys in both LoFC conditions compared with animals in the baseline and HiFC-stress conditions (p < 0.05 for all). The results demonstrate that a low-fat, low-cholesterol diet can halt plaque development, reduce arterial cholesterol content, and permit compensatory arterial enlargement, processes that were unaffected by social stress in this investigation.

Animals↗
PubMed1993

Effects of psychosocial stress on endothelium-mediated dilation of atherosclerotic arteries in cynomolgus monkeys.

The objectives of this study were to determine if psychosocial stress impairs dilation through endothelium-derived relaxing factor (EDRF)-mediated mechanisms and if this effect is long lasting. Monkeys were fed an atherogenic diet for 36 mo while in one of three experimental conditions: (a) stable social groups ("unstressed," n = 6); (b) unstable social groups for the first half of the experiment and stable groups for the second half ("early stress," n = 8); and (c) stable groups for the first half of the experiment and unstable groups for the second half ("late stress," n = 6). Iliac arteries were studied in organ chambers containing Krebs' buffer and 10(-6) M indomethacin. Arteries from the late stress group had impaired dilation (shift of the dose-response curve down and to the right) to acetylcholine and the calcium ionophore A23187 (for both, P < 0.05), but not to nitroprusside (P > 0.05), compared with unstressed or early stress monkeys. NG-methyl-L-arginine reduced the dose-response curve to both acetylcholine and A23187 in the unstressed group and resulted in similar vascular responses among all three groups (P > 0.05). We conclude that current, but not previous, exposure to chronic stress impairs endothelium-mediated dilation of atherosclerotic iliac arteries of cynomolgus monkeys through an EDRF-mediated mechanism.

Acetylcholine↗
PubMed1993

Effects of exercise and stress on body fat distribution in male cynomolgus monkeys.

The effects of exercise and stress on regional and whole body adiposity were examined in an established animal model of diet-induced coronary artery atherosclerosis, the cynomolgus monkey (Macaca fascicularis). A total of 79 adult male monkeys were assigned to four experimental groups after baseline stabilization and training: (i) exercise, stress, (n = 20); (ii) exercise, no stress (n = 20); (iii) sedentary, stress (n = 20); and (iv) sedentary, no stress (n = 19). The monkeys consumed an ad libitum diet containing 188 mg cholesterol per day with 43% of calories as saturated fat. Anthropometric measurements of regional and whole body adiposity were collected throughout the study. A subset (n = 40) of animals representing all four groups underwent computerized tomography (CT) scans at the end of the study to determine amounts of total abdominal, intra-abdominal and subcutaneous abdominal adipose tissue. Results indicate that, in general, stress interacted with exercise to affect anthropometric measurements of regional adiposity. In contrast, stress had independent and significant effects on the amount and distribution of abdominal fat as measured using CT. Stressed monkeys in both the exercise and sedentary groups had more intra-abdominal fat (and thus greater intra-abdominal-:subcutaneous abdominal fat ratios) than their nonstressed counterparts. There were no significant interactions between exercise and stress or exercise effects on abdominal fat distribution as measured by CT. These results support the belief that an arousal syndrome caused by chronic stress, and resulting in increased activity along the hypothalamo-adrenal axis, may play a role in the preferential deposition of fat in the abdomen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1992

Influence of age, sex, and family on Type A and hostile attitudes and behaviors.

We describe the influence of age, sex, and family on Type A and hostility indices that have been related to rates of coronary heart disease (CHD). The sample consisted of 120 girls and 95 boys (ages 6 to 18 years) and 141 women and 120 men (ages 31 to 62 years) from 142 families residing in an upper middle class community. Results showed little familial aggregation of Type A and hostility. Adults had higher Structured Interview (SI) Potential for Hostility ratings than did children, whereas children had higher Minnesota Multiphasic Personality Inventory (MMPI)-derived Hostility scores and SI Anger-In ratings than did adults. Male adults and male children had higher SI Potential for Hostility ratings and MMPI-derived Hostility scores than did their female counterparts. The heightened hostility of males may account, in part, for their heightened risk of CHD relative to females'.

Adolescent↗
PubMed1992

Reliable measures of behaviorally-evoked cardiovascular reactivity from a PC-based test battery: results from student and community samples.

This paper describes efforts to reduce measurement error in the assessment of cardiovascular reactivity by standardizing task requirements and by aggregating data across tasks and testing sessions. Using these methods, reliable measures of reactivity (.80 or greater) were obtained on five different measures of cardiovascular function (heart rate, systolic blood pressure, diastolic blood pressure, stroke volume, pre-ejection period) in samples of college students and community volunteers. Methodological limitations may have hampered previous efforts in this area. Current findings are consistent with a dispositional model of cardiovascular reactivity, and they suggest productive future strategies for obtaining reliable assessments.

Adult↗
PubMed1992

Acute cholesterol responses to mental stress and change in posture.

BACKGROUND: Serum lipid levels vary widely within individuals, but the causes of these fluctuations are poorly understood. One area of research concerns elevations in cholesterol concentration in response to emotional stress. In a laboratory-based experiment, we compared the effects of acute mental stress and postural change (standing) on serum cholesterol concentration. In addition, plasma volume was indirectly monitored to determine whether cholesterol changes with mental stress, if present, were a function of hemoconcentration. METHODS: Twenty-six men attended two laboratory sessions, each consisting of baseline (30 minutes), task (20 minutes), and recovery (30 minutes) periods. Subjects rested in the supine position during the baseline and recovery periods. During the task period of one session, subjects performed a mental task (Stroop test and mental arithmetic); during the other session, the subjects stood for the task period. RESULTS: Both mental stress and standing elicited significant elevations in heart rate, blood pressure, and plasma catecholamine concentrations, relative to the baseline and recovery periods. Both the mental and orthostatic tasks also significantly increased serum cholesterol concentration (by 0.10 and 0.57 mmol/L [3.7 and 21.9 mg/dL], respectively), as well as hemoglobin level and hematocrit. Cholesterol elevations with standing were reversible, while those resulting from mental stress persisted through the recovery period. When values were corrected for concomitant hemoconcentration, no net change in serum cholesterol level occurred during either task. CONCLUSIONS: Acute mental stress can produce rapid elevations in serum cholesterol concentration. It can also increase hemoglobin concentration and hematocrit (ie, reduce plasma volume). Therefore, increases in serum cholesterol level after acute mental stress are analogous to those with standing and may reflect hemoconcentration rather than altered lipoprotein metabolism.

Adolescent↗