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Biomedical subjects

S B Manuck

Publications and source records attributed to S B Manuck.

At least 55 records · Page 3Linked to original sources
PubMed1996

Hypertension and neuropsychological performance in men: interactive effects of age.

Potentially interactive effects of hypertension and age on the performance of neuropsychological and information processing tests were examined in 123 untreated hypertensive and 50 normotensive men. After covarying education, average alcohol consumption, trait anxiety, and depression scores, results indicated an interaction of age and hypertension. Young hypertensive men (23-40 years) scored significantly worse than young normotensive men on tests of attention/executive function and working memory; middle-aged hypertensive (41-56 years) and normotensive participants were not distinguished by any measures. Hypertensive men performed significantly more poorly than normotensive men on tests of manual dexterity. Results suggest that neuropsychological sequelae of hypertension are more pronounced in young than in middle-aged hypertensive individuals and are independent of various demographic, psychosocial, and alcohol-related factors.

Adult↗
PubMed1996

Interactive influences of ethnicity, gender and parental hypertension on hemodynamic responses to behavioral challenge.

To determine the independent and interactive influences of ethnicity, gender and parental hypertension on the magnitude and patterning of hemodynamic responses to standardized laboratory stressors, 112 normotensive, young adult African-American and Caucasian subjects (56 women, 56 men) completed a four-task protocol: three psychological stressors (the Stroop Color Word task, mental arithmetic and mirror tracing) and the forehead cold pressor test. Blood pressure (BP), heart rate (HR) and impedance derived measures of cardiac pre-ejection period and stroke volume were measured at rest and during each task; calculated indices of cardiac output and total peripheral resistance were also computed. Women responded to the psychological stressors with significantly larger increases in HR and cardiac output, less change in total peripheral resistance and greater attenuation of cardiac pre-ejection period than did men; however, blood pressure responses did not vary by gender, ethnicity or parental history of hypertension. Across tasks, African Americans showed larger elevations in total peripheral resistance than did Caucasians; conversely Caucasian subjects showed a more pronounced cardiac responsivity to stress, as evidenced by an elevated cardiac output and concomitant decrease in cardiac pre-ejection period, compared to their African-American counterparts. The ethnic differences in reactivity to psychological stressors were more apparent among males, while the gender differences were generally more pronounced among African Americans. Finally, the cold pressor test elicited larger increases in systolic blood pressure (SBP) among Caucasian subjects with family history positive (FH+), relative to family history negative (FH-) subjects, and also caused a greater reduction in HR among males compared to females.

Adult↗
PubMed1995

Long-term effects of chronic social stress on serotonergic indices in the prefrontal cortex of adult male cynomolgus macaques.

We examined the effects of chronic social stress and social rank on monamine concentrations in the prefrontal cortex (PFC) in adult male cynomolgus macaques (Macaca fascicularis). Seventy-five animals were housed in five-member social groups for 28 months and were exposed to three experimental conditions. A 'no-stress' condition was comprised of animals housed in groups of stable membership throughout the study. Animals assigned to a 'past-stress' condition had their group memberships reorganized at monthly intervals during the first (but not last) 14 months of the study, and a third 'recent-stress' condition consisted of social groups reorganized only during the last 14 months. At necropsy, the brains were collected and frozen at -70 degrees C until analyzed. Prefrontal orbital cortex was assayed for monoamines (serotonin (5-HT), dopamine (DA), norepinephrine (NE)), metabolites (5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), 3-methoxy-4-hydroxyphenethyleneglycol (MHPG)), and tryptophan using high-performance liquid chromatography with electrochemical detection. Animals in the past-stress condition had significantly lower PFC 5-HIAA concentrations compared to those in the no-stress condition (P < 0.05). PFC 5-HT concentrations of animals in the past-stress condition were significantly lower than those in the no-stress and recent-stress conditions (P < 0.01). The concentrations of DA, HVA, NE and MHPG were not altered. These data suggest that exposure to chronic social stress is associated with long-term selective reductions in serotonergic activity in the PFC. This effect may underlie the association in human beings between reduced serotonergic function and conditions such as pathological grief and posttraumatic stress disorder.

Animals↗
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

Neuroendocrine responses to fenfluramine challenge are influenced by exposure to chronic social stress in adult male cynomolgus macaques.

This study was designed to investigate the effect of chronic social stress on central serotonergic responsivity in adult male cynomolgus monkeys (Macaca fascicularis). The influences of social stress and dominance status (social rank) on adrenocorticotropin hormone (ACTH) and cortisol responses to acute administration of an indirect serotonergic agonist (fenfluramine) were evaluated in 75 cynomolgus macaques that were housed in five-member social groups for 28 mo. These groups either remained stable in composition (No-Stress) or had their composition periodically reorganized in the first (Early-Stress) or second (Late-Stress) halves of the study. At the end of the 23rd month, a fenfluramine challenge was done. Animals in the Late-Stress condition had significantly higher ACTH responses compared to those in the No-Stress condition (p < .05) and significantly higher cortisol responses compared to those in the Early-Stress condition (p < .05). No differences between dominant and subordinate animals in ACTH or cortisol responses to challenge were identified. These data suggest that social stress produces a "state"-related augmentation of hypothalamic-pituitary-adrenal responsivity to fenfluramine (serotonergic) challenge in cynomolgus macaques.

Adrenocorticotropic Hormone↗
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↗
PubMed1994

Cardiovascular reactivity in cardiovascular disease: "once more unto the breach".

Discussed here are conceptual and methodologic issues that bear on the role of behaviorally evoked cardiovascular reactivity in cardiovascular disease. It is argued that recent criticisms concerning the validity of cardiovascular reactivity as a stable dimension of individual differences arise from inadequacies of measurement prevalent in prior literature. With standardization of test stimuli and application of psychometric principles lo protocol development, assessment of reactivity are found to be highly reliable and, in turn, to demonstrate the dispositional nature of this construct. Recent studies also document an underlying heterogeneity of hemodynamic reactions to stress, with distinct cardiac and vascular components. Because hemodynamic adjustments show some plasticity under differing task conditions, responses seen in particular contexts reflect influences of both an individual-specific response potential and response-eliciting properties of the stimulus. On the question of disease relevance, it is concluded that cardiovascular reactivity cannot yet be considered an established risk factor for either coronary heart disease or hypertension. However, the preponderance of existing clinical, experimental. and epidemiologic evidence is consistent with such an association and warrants further study in the context or population-based, prospective investigation.

Journal Article↗
PubMed1993

Relationship of cardiovascular reactivity and anger expression to serum lipid concentrations in healthy young men.

The relationship between behaviorally evoked cardiovascular reactivity, preferred mode of anger expression, and serum lipid concentrations was examined in 63 healthy, young adult males. Subjects derived from three studies, each evaluating cardiovascular response to laboratory stressors. All participants completed the Spielberger Anger Expression Scale and provided fasting blood samples for lipid determinations. A significant negative correlation, calculated by meta-analytic procedures, was noted between a baseline-free measure of heart rate reactivity and high density lipoprotein-cholesterol (HDL-C) concentrations (r = -0.26, p = 0.05). However, the previously reported relationship between cardiovascular reactivity and elevated total serum cholesterol (TSC) was not found. Additionally, men scoring high on a self-report measure of the tendency to express anger outwardly had significantly higher HDL-C concentrations than men scoring low on this measure (r = 0.30, p = 0.02); when subjects were stratified by level of cardiovascular reactivity, this relationship was apparent only among those showing the greatest magnitude of heart rate and blood pressure responses to acute mental stress.

Adolescent↗
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↗