Biomedical subjects

M G Ziegler

Publications and source records attributed to M G Ziegler.

At least 55 records · Page 3Linked to original sources

PubMed1997

Low-frequency ultradian insulin rhythms are coupled to cardiovascular, autonomic, and neuroendocrine rhythms.

Plasma insulin levels were assayed to compare with earlier reported rhythms of the cardiovascular, autonomic, and neuroendocrine systems in 10 resting normal adults over 5-6 h. Our earlier report included time-series analysis for impedance cardiography measures of stroke volume, heart rate, cardiac output, thoracic fluid index, ejection velocity index, and ventricular ejection time; automated cuff measures of systolic, diastolic, and mean arterial pressures; the nasal cycle as a marker of lateralized autonomic tone; and indwelling venous catheters for sampling blood every 7.5 min to assay for adrenocorticotropic hormone, luteinizing hormone, epinephrine, and norepinephrine. Insulin was later assayed from the same plasma samples. Time-series analysis using the fast orthogonal search method of Korenberg detected insulin periodicities at ranges of 220-340, 115-145, 70-100, and 40-65, with significance across subjects at ranges of 115-145, 70-100, and 40-65 min. Significant periods for the other parameters were reported earlier at 220-340, 170-215, 115-145, 70-100, and 40-65 min, with periods at 115-145, 70-100, and 40-65 min dominating across parameters. These results suggest that insulin secretion has a common pacemaker (the hypothalamus) or a mutually entrained pacemaker with the autonomic, cardiovascular, and neuroendocrine systems.

Activity Cycles↗

PubMed1997

Sympathetic nervous system alterations in sleep apnea. The relative importance of respiratory disturbance, hypoxia, and sleep quality.

Numerous alterations in the sympathetic nervous system have been reported in patients with obstructive sleep apnea. It is unclear whether such alterations can be attributed to the respiratory disturbance itself, the resulting hypoxia, or disruption of sleep. We examined urinary norepinephrine levels in 45 individuals with varying amounts of respiratory disturbance and sleep disruption. All were of similar age (40 to 60 years) and body weight (100 to 160% ideal body weight), and all were free from antihypertensive medications that could influence norepinephrine levels. Twenty-four-hour urinary norepinephrine levels were correlated with respiratory disturbance index (r = 0.39, p < 0.01) and mean oxygen saturation (r = -0.36, p < 0.05). These variables, together with the time in slow-wave sleep, accounted for a statistically significant but modest percentage of the variance in urinary norepinephrine (R2 = 0.19, p < 0.05). However, the variables were so tightly intercorrelated that no single variable independently predicted norepinephrine levels in multiple regression analysis.

Adult↗

PubMed1997

Neuropeptide Y-mediated pressor responses following high-frequency stimulation of the rat sympathetic nervous system.

Neuropeptide Y (NPY) is a potent pressor agent that is stored in the sympathetic nerves. In several species, NPY release is augmented when sympathetic impulse frequencies increase. We investigated the extent to which NPY contributes to the pressor response to high- and low-frequency electrical stimulation. Rats were pithed, and the sympathetic trunk was stimulated at either 20 or 3 Hz in the presence or absence of antagonists of NPY and alpha and beta adrenergic receptors. The 20-Hz stimulation raised plasma NPY levels, but the 3-Hz stimulation did not. The 20-Hz stimulation caused marked pressor responses that were maintained for several minutes after the end of stimulation regardless of whether rats were pretreated with adrenergic blockers. The NPY antagonists BIBP 3226 and 1229U91 reduced the size of the pressor response that followed 20 Hz stimulation by >50%. The rapid blood pressure spikes that occur during electrical stimulation are attenuated by alpha adrenergic but not by NPY antagonists. There is a prolonged pressor response after high-frequency stimulation of the sympathetic trunk in pithed rats that begins after 1 to 2 min of stimulation and lasts approximately 10 min after the end of stimulation. At least half of this pressor response is mediated by NPY.

Amino Acid Sequence↗

PubMed1996

The effects of the menstrual cycle, race, and gender on adrenergic receptors and agonists.

OBJECTIVE: To examine possible effects of race, sex, and the menstrual cycle on adrenergic receptors (beta 2 and alpha 2) and agonists. METHODS: Sixty-three normotensive black men and women and white men and women were studied twice, approximately 6 weeks apart. Women were studied once during the follicular phase and once during the luteal phase of the menstrual cycle. beta 2-Adrenergic receptors and adenylate cyclase activity were examined on lymphocytes, and alpha 2-adrenergic receptors were examined on platelets. Norepinephrine and epinephrine were determined in plasma. RESULTS: Women showed greater lymphocyte beta 2-receptor sensitivity (isoproterenol-stimulated cyclic adenosine monophosphate; p = 0.009). Women also showed greater postreceptor adenylate cycle activity independent of the beta-receptor (forskolin stimulation; p = 0.006). When these differences were controlled for, the gender-related differences in beta 2-receptor sensitivity were no longer evident. Black women had a reduced beta 2-receptor sensitivity in the luteal phase compared with the follicular phase, whereas white women showed no significant change (p = 0.018). Black subjects had lower lymphocyte beta 2-receptor density (Bmax) values than white subjects (p = 0.047). There were no significant effects on alpha 2-adrenergic receptors. CONCLUSION: The findings suggest that although there is no generalized effect of the menstrual cycle on adrenergic receptors in white women, such an effect may occur in black women. The findings also suggest that previously reported gender-related differences in beta 2-receptor sensitivity may be due to gender-related differences in postreceptor activity and not the beta 2-receptor per se.

Adrenergic beta-Agonists↗

PubMed1996

Altered cardiac contractility in sleep apnea.

Adrenergic regulation in sleep apnea is a complex process because adrenergic physiology is difficult to summarize with one measure. Furthermore, the role of the adrenergic system in sleep apnea is often confounded with hypertension, making interpretation difficult in hypertensive apneics. Sixty-six people with and without apnea and/or hypertension (all were off antihypertensive medication) participated in this study. Cardiac beta-adrenergic drive, as assessed by systolic time intervals, was examined at rest and in response to a mild laboratory stressor. These measures of cardiac contractility included the pre-ejection period, electrical systole (QT) interval and the cardiac acceleration index. At rest, apneics showed elevated myocardial contractility on all measures (p = 0.001). In response to the laboratory stressor, non-apneics showed an increase in cardiac beta-adrenergic drive (p = 0.001), whereas the contractility in apneics did not change or decreased relative to baseline. These findings suggest disrupted cardiac adrenergic regulation in people with sleep apnea. Apnea appears to increase resting sympathetic activity and down regulate beta2-adrenergic receptors. The downregulation of cardiac beta-adrenergic receptor activity may explain the inability of people with sleep apnea to respond with appropriate cardiac contractility to a mild perturbation.

Adult↗

PubMed1996

Ultradian rhythms of autonomic, cardiovascular, and neuroendocrine systems are related in humans.

Autonomic, cardiovascular, and neuroendocrine activities were monitored for 5-6 h in 10 normal adult resting humans (8 males, 2 females). The nasal cycle, a measure of lateralized autonomic tone, was measured at 4 Hz. Impedance cardiography (BoMed NCCOM3) was used to measure cardiac output, thoracic fluid index, heart rate, ejection velocity index, stroke volume, and ventricular ejection time (averages of 12 heart beats). Systolic, diastolic, and mean arterial pressures were measured with an automated cuff at 7.5-min intervals. Separate blood samples were taken every 7.5 min simultaneously from both arms with the use of indwelling venous catheters. Assays for adrenocorticotropic hormone, luteinizing hormone, norepinephrine, epinephrine, and dopamine were performed on samples from each arm. Time-series analysis, using the fast orthogonal search method of Korenberg, was used to detect variance structure. Significant spectral periods were observed in five windows at 220-340, 170-215, 115-145, 70-100, and 40-65 min. The greatest spectral power was observed in the lower frequencies, but periods at 115-145, 70-100, and 40-65 min were common across variables. Significant correlation coefficients for linear regressions of all paired variables in each subject were observed in 38.87% of the comparisons (subject range, 18.05-48-9.70%) with r > 0.30. These results suggest that either a common oscillator (the hypothalamus) or mutually entrained oscillators regulate these systems.

Activity Cycles↗

PubMed1996

Menstrual cycle effects on catecholamine and cardiovascular responses to acute stress in black but not white normotensive women.

This study examined cardiovascular and catecholamine responses to two standardized laboratory stressors in 33 healthy age- and weight-matched black and white normotensive women (mean age, 32 years) during two phases of the menstrual cycle. Subjects were studied in a randomized order at the same time of day on two separate occasions approximately six weeks apart, once during the follicular phase (days 7 to 10 after menses) and once during the luteal phase (days 7 to 10 after the leutenizing hormone surge) of the menstrual cycle. Black women has higher systolic (P=.01) and diastolic (P=.01) pressures compared with white women. Black women showed greater diastolic pressure (P <.01) and plasma epinephrine (P <.05) responses to stress during the follicular compared with the luteal phase of the menstrual cycle; white women showed no significant changes in these variables. The findings extend the literature on race differences in responsivity to stress and indicate that in contrast to white women, reproductive hormones do influence cardiovascular and catecholamine responsivity to stress in black women.

Adult↗

PubMed1996

Sertraline does not alter the beta-adrenergic blocking activity of atenolol in healthy male volunteers.

UNLABELLED: A double-blind, placebo-controlled, randomized, crossover study was conducted to determine the effect of sertraline on the beta-adrenergic blocking activity of atenolol in 10 healthy male volunteers. METHOD: To assess the existence of any possible pharmacodynamic interaction between sertraline and atenolol, the effect of sertraline and placebo on the dose of intravenous isoproterenol required to increase heart rate by 25 beats per minute (bpm; chronotropic dose25 [CD25]) and the change in heart rate during exercise in atenolol-treated subjects were determined. RESULTS: The mean CD25 of isoproterenol was 2.00 micrograms after administration of placebo plus atenolol 50 mg and 2.03 micrograms after administration of sertralnie 100 micrograms plus atenolol 50 mg. The mean heart rate during exercise testing decreased by 29 bpm after sertraline plus atenolol administration and by 31 bpm after placebo plus atenolol administration. Analysis of variance indicated no statistically significant treatment or sequence effects. Only 1 subject experienced an adverse event--a mild headache after administration of sertraline plus atenolol. No clinically significant electrocardiograph changes were observed after sertraline or placebo administration. CONCLUSION: The results of this study demonstrate that sertraline does not alter the beta-blocking activity of atenolol.

1-Naphthylamine↗

PubMed1995

The accuracy of drug information from pharmaceutical sales representatives.

OBJECTIVE: To provide quantitative data about the accuracy of the information about drugs presented to physicians by pharmaceutical sales representatives. DESIGN: One hundred six statements about drugs made during 13 presentations by pharmaceutical representatives were analyzed for accuracy. Statements were rated inaccurate if they contradicted the 1993 Physicians' Desk Reference or material quoted or handed out by the sales representative. SETTING: University teaching hospital. RESULTS: Twelve (11%) of 106 statements about drugs were inaccurate. All 12 inaccurate statements were favorable toward the promoted drug, whereas 39 (49%) of 79 accurate statements were favorable (P = .005). None of 15 statements about competitors' drugs were favorable, but all were accurate, significantly P < .001) differing from statements about promoted drugs. In a survey of 27 physicians who attended these presentations, seven (26%) recalled any false statement made by a pharmaceutical representative, and 10 (37%) said information from the representatives influenced the way they prescribed drugs. CONCLUSIONS: Eleven percent of the statements made by pharmaceutical representatives about drugs contradicted information readily available to them. Physicians generally failed to recognize the inaccurate statements.

Commerce↗

PubMed1995

Lymphocyte subset redistribution in response to acute experimental stress: effects of gender, ethnicity, hypertension, and the sympathetic nervous system.

This study examined demographic and adrenergic characteristics associated with enumerative immune responses to acute laboratory stress. Lymphocyte subsets and plasma catecholamines were measured in 110 subjects at rest and following a naturalistic speaking stressor. Lymphocyte beta 2-adrenergic receptor sensitivity and density were measured at rest. The speaking task caused marked increase in natural killer cells, T-suppressor/cytotoxic cells, total WBC, norepinephrine, and epinephrine and decreases in T-helper cells, B cells and the T-helper/suppressor ratio. Multiple regression analyses demonstrated that, in general, cellular immune responses were best predicted by a combination of lower basal norepinephrine, higher beta 2-adrenergic receptor sensitivity, and a greater stress-induced increase in norepinephrine. The findings suggest that traditional epidemiologic characteristics such as gender, ethnicity, and mild hypertension have limited influence on lymphocytosis. Rather, interindividual differences in sympathetic nervous system characteristics play a more prominent underlying role in acute cellular immune system activation.

Adult↗

PubMed1995

Enumerative immune changes following acute stress: effect of the menstrual cycle.

This study examined enumerative immune and catecholamine measures and their response to a speaking stressor in 20 healthy women during two phases of the menstrual cycle. Subjects were studied at the same time of day on two separate occasions approximately 6 weeks apart, once during the follicular phase (Days 7-10 following menses) and once during the luteal phase (Days 7-10 following the LH surge) of the cycle. The stressor was associated with significantly increased CD8 cells (p < .001). NK cells (CD16, CD56, and CD57, p < .001), and plasma norepinephrine (p < .01) and decreased CD4/CD8 ratio (p < .001). There were no significant main effects for menstrual phase nor significant interactions for menstrual phase by task for any dependent variable. Baseline and stress test-retest correlation coefficients were similar to those reported in the literature for men and indicate a moderate test-retest reliability. Change score test-retest correlation coefficients were consistently smaller and only CD56 (r = .49) and the CD4/CD8 ratio (r = .55) correlated significantly. The findings suggest that the changes in reproductive hormones associated with the menstrual cycle have no appreciable effect on lymphocyte numbers or their response to acute stress. Given estrogen's long-term duration of action, it may be that their menstrual cycle does not afford an adequate window of time to scrutinize reproductive hormone effects on the immune functioning.

Adult↗

PubMed1995

Reduced beta 2-receptor mediated vasodilation in African Americans.

It is well recognized that African Americans have a higher prevalence of cardiovascular disease than White Americans although the underlying mechanisms are not entirely understood. This study was perfumed to evaluate racial differences in the chronotropic and vasodilatory effects of the beta-receptor agonist, isoproterenol. We compared cardiovascular responses to intravenous infusion of isoproterenol in 27 African Americans and 27 White men and women. African Americans showed significantly smaller beta 2-receptor mediated falls in diastolic pressure than Whites. In contrast, isoproterenol produced similar increases in heart rate in both races. The findings suggest that African Americans have decreased beta 2-receptor mediated vasodilatory capacity, and may help explain the higher prevalence of hypertension and cardiovascular disease in African Americans compared to Whites.

Adult↗

PubMed1995

Relationship of insulin, race, and hypertension with hemodynamic reactivity to a behavioral challenge.

Insulin is a modulator of blood pressure and may play a role in the pathogenesis of hypertension. This study examined the relationship between fasting insulin level and cardiovascular reactivity in hypertensive and normotensive black and white patients. Eighty-one patients were studied after 3 days of hospitalization on an isocaloric diet providing 200 mmol Na+ and 100 mmol K+ per day. Fasting insulin levels were determined on the morning of the second hospital day; a median split was used to determine high- and low-insulin groups. On the next day of hospitalization we examined blood pressure and hemodynamic responses to a speaking challenge. Hemodynamic responses were determined with impedance cardiography. Reactivity was studied as the percentage change from resting baseline. There were significant race by blood pressure level interactions for systolic and diastolic blood pressure reactivity (P < or = .01). Black hypertensives showed more blood pressure reactivity than either the white hypertensives or the white normotensives; black normotensives had less blood pressure reactivity than the other groups. Insulin grouping interacted with blood pressure level and race on the reactivity of the underlying hemodynamic measures (total peripheral resistance, stroke volume, and heart rate; P < or = .02). Fasting insulin level had no relationship to blood pressure reactivity. On the other hand, insulin level interacted with blood pressure level and race on the underlying hemodynamics controlling blood pressure, namely total peripheral resistance and stroke volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Factitious pheochromocytoma: novel mimickry by Valsalva maneuver and clues to diagnosis.

Factitious pheochromocytoma usually occurs in patients surreptitiously ingesting adrenergic medications. We encountered a case of factitious pheochromocytoma where in the subject mimicked hemodynamic (profound hypertension) and biochemical (plasma catecholamine elevation) manifestations of the illness by consciously altering autonomic function with Valsalva maneuver. Clues to this presentation included visible performance of Valsalva maneuver, marked disparity between blood pressures recorded in the presence and absence of the subject's knowledge, normal urinary catecholamine and metabolite excretion, and normal plasma chromogranin A. We reproduced, in part, the hemodynamic and biochemical manifestations of this presentation with Valsalva maneuver in healthy subjects.

Adrenal Gland Neoplasms↗

PubMed1995

Assessment of baroreflex control from beat-to-beat blood pressure and heart rate changes: a validation study.

In this study, we tested the validity of a new method designed to estimate baroreflex control of heart rate from spontaneous changes in systolic pressure and pulse interval. This method was compared with a conventional method of assessing baroreflex control through measuring reflex adjustments in pulse interval associated with pharmacological manipulations of blood pressure. The estimates of baroreflex control derived from the two methods were significantly correlated; however, only the estimate derived using pharmacological changes in pressure detected significant impairment of baroreflex control in patients with damage to baroafferents produced by radiation for oropharyngeal cancer. Analysis of spontaneous changes in pressure and pulse interval therefore provide a meaningful estimate of baroreflex control of heart rate that is, however, less sensitive than estimates obtained using pharmacological manipulations in pressure.

Adult↗

PubMed1995

Racial differences in epinephrine and beta 2-adrenergic receptors.

This study examined the effects of ethnicity and hypertension on beta 2-adrenergic receptors and on plasma catecholamines in a group of 77 unmedicated mildly hypertensive and normotensive men. Black hypertensive subjects had the most sensitive and white hypertensive subjects the least sensitive beta-receptors (as assessed by isoproterenol-stimulated cyclic AMP in lymphocytes [P = .02]). In contrast, postreceptor adenylate cyclase activation (as assessed by forskolin stimulation) was similar among groups. As with beta-receptor sensitivity, black hypertensive subjects had the highest beta-receptor density and white hypertensive subjects the lowest (P = .03). Blacks demonstrated lower plasma epinephrine values compared with whites (P = .03). Across all subjects, plasma epinephrine was negatively correlated with beta-receptor density (r = -.26, P < .05) and sensitivity (r = -.25, P < .05). There were no group differences in binding affinity to the beta-antagonist iodopindolol. The findings support the notion of increased beta-adrenergic receptors in hypertension in blacks.

Adult↗

PubMed1995

Divergent effects of dihydropyridine and phenylalkylamine calcium channel antagonist classes on autonomic function in human hypertension.

Calcium channel antagonists differ by class in reported frequency of side effects that suggest reflex sympathoadrenal activation. Do such differences result from differential effects on autonomic and baroreflex function? The present study compared acute and chronic effects of two classes of calcium channel antagonists, the dihydropyridine type (felodipine) and the phenylalkylamine type (verapamil), on efferent sympathetic outflow and baroreflex slope in 15 essential hypertensive subjects. Blood pressure, heart rate, hemodynamics, and biochemistries were determined at baseline and after acute (first dose) and chronic (4 weeks) administration of the drugs versus placebo. Acutely, felodipine caused a greater decrease in blood pressure associated with a larger decline in systemic vascular resistance than the corresponding effects produced by verapamil. Chronically, there were similar, significant declines in blood pressure (P = .001) and systemic vascular resistance (P = .001) after each drug. Acutely, increased sympathetic activity after felodipine was suggested by reflex tachycardia (from 69 +/- 3 to 74 +/- 2 beats per minute, P = .014) and elevation of plasma norepinephrine (from 264 +/- 25 to 323 +/- 25 pg/mL, P = .037), whereas after verapamil the corresponding changes were closely similar to those after placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗

PubMed1995

Chromogranin A in human hypertension. Influence of heredity.

Multiple heritable traits are associated with essential (genetic) hypertension in humans. Because chromogranin A is increased in both human and rodent genetic hypertension, we examined the influence of heredity and blood pressure on chromogranin A in humans. In estimates derived from among- and within-pair variance in monozygotic versus dizygotic twins, plasma chromogranin A displayed significant (F15,18 = 2.93, P = .016) genetic variance (sigma 2 g), and its broad-sense heritability was high (h2B = 0.983). Plasma chromogranin A was increased in essential hypertension (99.9 +/- 6.7 versus 62.8 +/- 4.7 ng/mL, P < .001) but was influenced little by genetic risk for (family history of) hypertension (in normotensive or hypertensive subjects), by race, or by several antihypertensive therapies (angiotensin-converting enzyme inhibitor, diuretic, or beta-adrenergic antagonist). In normotensive subjects at genetic risk for essential hypertension, neither basal nor sympathoadrenal stress-evoked chromogranin A differed from values found in subjects not at risk. In established essential hypertension, plasma chromogranin A responses to adrenal medullary (insulin-evoked hypoglycemia) or sympathetic neuronal (dynamic exercise) activation were exaggerated, whereas responses to sympathoadrenal suppression (ganglionic blockade) were diminished, suggesting increased vesicular stores of chromogranin A and an adrenergic origin of the augmented chromogranin A expression in this disorder. We conclude that plasma chromogranin A displays substantial heritability and is increased in established essential hypertension. Its elevation in established hypertension is associated with evidence of increased vesicular stores of the protein and with adrenergic hyperactivity but is influenced little by customary antihypertensive therapies. However, the chromogranin A elevation is not evident early in the course of genetic hypertension.

Adrenal Medulla↗