Search PubMed⌕ Search

Biomedical subjects

S B Manuck

Publications and source records attributed to S B Manuck.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1991

Alterations in specific antibody production due to rank and social instability.

Separate studies examined the influence of the social environment of male cynomolgus macaques on primary and secondary antibody responses to immunization with tetanus toxoid. All animals showed evidence of both primary and secondary anti-tetanus antibody response. In the first study, subordinate animals had a greater primary antibody response to tetanus toxoid, while a single social reorganization (acute stressor) did not influence the response. In the second study, social rank was not associated with the secondary antibody response but repeated social reorganizations (chronic stressor) resulted in a greater level of specific antibody production in comparison to nonreorganized controls. These effects could not be accounted for on the basis of nonspecific differences in total serum IgG or serum albumin.

Animals↗
PubMed1991

Learning and memory function in men with untreated blood pressure elevation.

Learning and memory processes were compared in 20 men with untreated blood pressure elevation and 20 normotensive control subjects matched for age, education, and average alcohol consumption. Subjects were identified from a larger sample of 469 factory workers who had participated in an epidemiologic investigation. Three measures (e.g., Symbol-Digit Learning Test [Ryan & Butters, 1980] and Visual Reproductions-Immediate and Delayed Recall [Wechsler, 1945] ) from a previously administered test battery were chosen for comparison on the basis of statistical power calculations. Results indicate that relative to normotensive control subjects, men with elevated blood pressure performed more poorly on all three tests. These results are independent of other known influences on neuropsychological performance and are likely a consequence of elevated blood pressure.

Adult↗
PubMed1991

Neuropsychological correlates of hypertension: review and methodologic considerations.

Essential hypertension is a chronic disorder having many potential physical and behavioral sequelae. This article evaluates the impact of hypertension on neuropsychological test performance. First, cross-sectional and longitudinal studies that examine the neuropsychological correlates of hypertension are reviewed. In general, hypertensives are found to perform more poorly than normotensives, particularly on tests of memory, attention, and abstract reasoning, and less consistently on tests of perception, constructional ability, mental flexibility, and psychomotor speed. Next, the influence of variables that may moderate relationships between hypertension and neuropsychological performance--such as age, education, and medication usage--are examined. Finally, potential mechanisms, both physiological and psychological, underlying associations between hypertension and neuropsychological performance are discussed.

Brain↗
PubMed1991

Neurobehavioral effects of antihypertensive medications.

Although millions of hypertensive individuals receive chronic treatment with antihypertensive medication, the effect on the central nervous system by these drugs is poorly understood. Such treatment, while generally well tolerated, frequently produces symptoms of drowsiness, weakness, altered memory and impaired concentration. In addition to subjective evidence derived from patient reports, a large number of investigations have now been published which attempt to objectively assess the influence of antihypertensive medication on behavioral or cognitive performance. This paper summarizes and critically evaluates experimental studies of the effect of antihypertensive medication on subjects' performance of neuropsychological tasks and reviews the pharmacologic mechanisms by which these drugs may affect behavior. The literature is incomplete in its assessment of all domains of neuropsychological performance and all drug classes, and methodologic deficiencies are common. Nonetheless, the consensus of all studies and the findings of well-designed studies in particular do not identify any notable areas of performance impairment in patients receiving antihypertensive medication. Moreover, results suggest that, in certain instances, drug treatment may even enhance performance. In light of the limitations of the literature, however, an adequate understanding of the effects of antihypertensive therapy on behavioral functioning awaits completion of large, well-designed investigations including all major drug classes and thorough neurobehavioral assessments.

Adrenergic beta-Antagonists↗
PubMed1991

Neither awake nor sleep blood pressures better predict target-organ effect.

We sought to assess the strengths of commonly used ambulatory blood pressure (ABP) parameters as predictors of transmitral flow/velocity ratio (E/A) and the dimensions that govern the left ventricular (LV) mass index. ABP, E/A, and LV dimensions were assessed in 47 subjects, with inclusion of 45 in the final data analysis. The results of four weekly (96 h total) ABP studies were averaged for each subject. No single ABP parameter immerged as a "best predictor." Furthermore, casual blood pressures taken at the beginning of the echo examination had predictive strength for LV mass which was similar to that of the ambulatory data. In the present study, neither awake nor sleep ABPs differed significantly with respect to correlations with indices of LV structure.

Adult↗
PubMed1991

Psychosocial factors impair vascular responses of coronary arteries.

BACKGROUND: Four sets of monkeys were used to examine the effect of chronic psychosocial disruption and diet on dilator responses of coronary arteries. METHODS AND RESULTS: One set consisted of monkeys consuming monkey chow and living in a stable social setting (nonatherosclerotic controls, n = 6). Three sets consumed an atherogenic diet for 14 months followed by one of three treatments for the next 16 months: 1) a high-cholesterol diet and housed in unstable social groups (n = 9); 2) a low-cholesterol diet and housed in unstable (n = 8); or 3) stable groups (n = 10). Quantitative coronary angiography revealed that intracoronary infusion of acetylcholine resulted in a change of diameter (versus infusion of 5% dextrose in water) of +4 +/- 1% in control monkeys and -11 +/- 4% in unstable monkeys consuming a high-cholesterol diet (p less than 0.05). In monkeys consuming the cholesterol-lowering diet, the change in artery diameter was +2 +/- 4% in stable and -10 +/- 4% in unstable social conditions (p less than 0.05) despite a similar plaque size (0.4 +/- 0.2 and 0.5 +/- 0.1 mm2) and total plasma cholesterol concentrations (179 +/- 9 and 172 +/- 6 mg/dl), respectively. The arterial response to nitroglycerin was similar among all groups of monkeys. CONCLUSIONS: We conclude that chronic social disruption is associated with relative arterial constriction in response to acetylcholine in atherosclerotic monkeys consuming a cholesterol-lowering diet.

Animals↗
PubMed1991

Endothelial dysfunction in response to psychosocial stress in monkeys.

The current study was designed to evaluate the effects of a disrupted social environment on the endothelial integrity of various vascular segments in male cynomolgus monkeys (Macaca fascicularis). Each of 20 single-caged adult monkeys was fed a diet comparable to a person's ingestion of 240 mg cholesterol/day for a 10-week baseline period and then was introduced as a stranger into a four-member social group for 3 days. Half of the monkeys received a beta-adrenergic blocking agent (metoprolol) via subcutaneous implant 2 days before and during group housing. The social manipulation produced persistent sympathetic arousal as evidenced by significantly elevated heart rates among untreated monkeys (p less than 0.01) but not among their metoprolol-treated counterparts, whose heart rate declined (p less than 0.05). After the social manipulation, all monkeys were necropsied and evaluated for endothelial incorporation of immunoglobulin G (as an indicator of cell death), endothelial cell replication, the presence of adherent leukocytes, and arterial low density lipoprotein permeability and concentration. At branching sites in the thoracic aorta, immunoglobulin G incorporation and endothelial cell replication were significantly greater in untreated monkeys than in metoprolol-treated monkeys (p less than 0.01 for both analyses); no differences existed at nonbranch sites. Endothelial cell replication in the coronary arteries (where immunoglobulin G incorporation was not examined) was also greater among untreated than among metoprolol-treated monkeys. No significant differences were observed between treatment groups in arterial low density lipoprotein permeability or leukocyte adherence; estimates of arterial low density lipoprotein concentrations were higher among untreated than among metoprolol-treated monkeys, but only in the abdominal portion of the aorta. These results indicate that social disruption is associated with both sympathetic nervous system arousal and indexes of endothelial dysfunction, effects that may be prevented by treatment with a beta-adrenergic blocking agent.

Animals↗
PubMed1991

Social behavior and gender in biomedical investigations using monkeys: studies in atherogenesis.

We review the use of socially housed cynomolgus monkeys (Macaca fascicularis) in biomedical research with emphasis on studies of atherosclerosis, particularly in the two specific domains of atherosclerosis investigation for which nonhuman primates are especially well-suited as animal models: gender differences and psychosocial influences. We found that the presence of normal ovarian function prevented exacerbation of diet-induced coronary artery atherosclerosis in female monkeys. However, any manipulation or condition which impaired ovarian function tended to diminish or abolish this "female" protection. Among group-housed female monkeys, low social status was accompanied by ovarian dysfunction and, not surprisingly, by exacerbated coronary artery atherosclerosis as well. Surgical menopause (ovariectomy) also induced exacerbation of coronary atherosclerosis in monkeys, a situation which was prevented by estrogen replacement therapy. Conversely, pregnancy (a hyperestrogenic state) resulted in markedly diminished atherosclerosis. A somewhat different pattern of atherogenesis emerged among socially-housed males. Here, socially dominant animals developed exacerbated coronary artery atherosclerosis, but only under conditions of social stress (viz., disruption caused by periodic reorganization of social group membership). We hypothesized that exposure to repeated group reorganizations provoked activation of the sympathetic nervous system among dominant animals; in turn, the hemodynamic and metabolic concomitants of sympathetic activation may have damaged the coronary arteries of these monkeys, potentiating atherogenesis. To test this hypothesis, males were housed in unstable social groupings, with half of the monkeys administered a beta-adrenergic blocking agent (to attenuate heart rate and blood pressure responses to stress). The beta-blocker inhibited atherosclerosis, but only among those animals behaviorally predisposed to develop exacerbated lesions (i.e. dominant monkeys). These results support the view that monkeys are suitable research models of atherosclerosis, a disease that affects millions of humans.

Animals↗
PubMed1991

Role of sympathoadrenal medullary activation in the initiation and progression of atherosclerosis.

Clinical and epidemiological investigations provide evidence that psychosocial factors influence the development of coronary heart disease and underlying atherosclerosis, an association that appears to be independent of the effects of other coronary disease risk factors. It has been hypothesized that sympathoadrenal medullary activation mediates behavioral influences on coronary disease, perhaps by potentiation of atherogenesis. This article summarizes four recent studies of the effects of psychosocial stress and sympathetic arousal on atherogenesis in cynomolgus monkeys (Macaca fascicularis) and rabbits. It is reported that socially dominant male monkeys, when fed an atherogenic diet and subjected to periodic social disruption, developed markedly worsened coronary atherosclerosis in comparison with subordinate monkeys; this effect may have been sympathetically mediated, as it was inhibited in similarly aggressive monkeys treated with a beta-adrenergic blocking agent. Studies using chow-fed rabbits demonstrated that exposure to chloralose anesthesia (an agent that provokes profound sympathetic activation) induced endothelial injury (indicated by intracellular accumulation of immunoglobulin G in the aortic endothelium) and abnormal (increased) platelet accumulation. The further observation that these effects were inhibited under beta-adrenoceptor blockade implicates sympathoadrenomedullary arousal in the initiation of atherogenesis. Additionally, sympathetically mediated endothelial damage and increased platelet accumulation occurred preferentially at circumostial sites in the rabbits, a finding consistent with the hypothesis that the hemodynamic concomitants of sympathetic activation contribute to atherogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗
PubMed1991

Prospective study of ambulatory monitoring and echocardiography in borderline hypertension.

This study was done to evaluate prospectively whether ambulatory blood pressure recordings (AMB) (Spacelabs) would more accurately predict increases in left ventricular mass (LVMI) than did blood pressures measured by a nurse in the absence of a physician, using a random zero sphygmomanometer (RZ) and an automated oscillometric digital device (BPI). One hundred patients being followed by their family physician with a diagnosis of borderline hypertension with at least two office diastolic readings of 90-100 mmHg were studied at baseline and every six months for two years with RZ, BPI, and AMB; echocardiography was repeated annually. Over sixty percent of the patients were normotensive in the research unit by AMB, BPI, and RZ at entry. At entry 24% of patients had increased LVMI greater than 110 g/m2 (left ventricular enlargement, LVE) and at 2 years 32% had LVE. Stepwise linear regression was used to determine which measurement was most predictive of LVE at two years. It showed that the most predictive were baseline echo LVMI and BPI systolic pressure. These two variables predicted 45% of the risk with no other variables contributing significantly. However, when BPI was removed, AMB systolic pressure contributed significantly, though the strength of prediction was reduced to 40%. In a subset of 40 patients who underwent mental stress with mental arithmetic and mirror tracing, the magnitude of systolic pressure elevation during mental stress correlated significantly with LVE over 2 years (R = 0.54, p less than 0.001).

Adolescent↗