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Biomedical subjects

M G Ziegler

Publications and source records attributed to M G Ziegler.

At least 37 records · Page 2Linked to original sources
PubMed2000

Heredity and the autonomic nervous system in human hypertension.

Because the complex phenotype of human hypertension is at least in part genetically determined, how individual genes ultimately contribute to the disease is not well understood. By contrast, intermediate phenotypes are traits associated with complex disease, but which may display simpler genetic properties such as greater heritability, more consistent and earlier penetrance and bimodality, and may suggest particular candidate susceptibility genes. Because autonomic nervous system activity is altered in hypertension, we examined biochemical, physiologic, and pharmacologic autonomic traits that fulfill at least some of these properties. Such biochemical, physiologic, or pharmacologic autonomic traits may be especially valuable as phenotypic anchor points in linkage or association studies probing the genetic basis of human hypertension.

Autonomic Nervous System↗
PubMed2000

False positive head-up tilt: hemodynamic and neurohumoral profile.

OBJECTIVES: This study examined differences in mechanisms of head-up tilt (HUT)-induced syncope between normal controls and patients with neurocardiogenic syncope. BACKGROUND: A variable proportion of normal individuals experience syncope during HUT. Differences in the mechanisms of HUT-mediated syncope between this group and patients with neurocardiogenic syncope have not been elucidated. METHODS: A 30-min 80 degrees HUT was performed in eight HUT-negative volunteers (Group I), eight HUT-positive volunteers (Group II) and 15 patients with neurocardiogenic syncope. Heart rate and blood pressure (BP) were monitored continuously. Epinephrine and norepinephrine plasma levels, as well as left ventricular dimensions and contractility determined by echocardiography, were measured at baseline and at regular intervals during the test. RESULTS: The main findings of this study were the following: 1) All parameters were similar at baseline in the three groups; and 2) During tilt: a) the time to syncope was shorter in Group III than in group II (9.5 +/- 3 vs. 17 +/- 3 min p < 0.05); b) there was an immediate, persisting drop in mean BP in Group III; c) the decrease rate of left ventricular end-diastolic dimensions was greater in Group III than in Group II or Group I (-1.76 +/- 0.42 vs. -0.87 +/- 0.35 and -0.67 +/- 0.29 mm/min, respectively, p < 0.05); d) the leftventricular shortening fraction was greater in Group III than in the other two groups (39 +/- 1 vs. 34 +/- 1 and 32 +/- 1%, respectively, p < 0.05); and e) although the norepinephrine level remained comparable among the groups, there was a significantly higher peak epinephrine level in Group III than in Group II and Group I (112.3 +/- 34 vs. 77.6 +/- 10 and 65 +/- 12 pg/ml, p < 0.05). CONCLUSIONS: Mechanisms of syncope during HUT appeared to be different in normal volunteers and patients with neurocardiogenic syncope. In the latter, there was evidence of an impaired vascular resistance response from the beginning of the orthostatic challenge. Furthermore, in the patients there was more rapid peripheral blood pooling, as indicated by the echocardiographic measurements of left ventricular end-diastolic changes, leading to more precocious symptoms. In syncopal patients, the higher level of plasma epinephrine probably mediated the increased cardiac contractility and possibly contributed to the impaired vasoconstrictive response.

Adult↗
PubMed2000

Ontogeny of epinephrine metabolic pathways in the rat: role of glucocorticoids.

Recent studies suggest that the initial expression of adrenal phenylethanolamine N-methyltransferase (PNMT) and epinephrine (E) are dependent upon stimulation of adrenal glucocorticoid receptors. However, evidence suggests that the expression of heart and brain PNMT is independent of glucocorticoids. We measured PNMT activity and E levels in adrenal, heart and head over the latter half of gestation in rat fetuses treated chronically with glucocorticoids, and in normal controls. Chronic glucocorticoid treatment ending on embryonic day (e)12 did not affect heart, head or trunk PNMT activity or E levels. In contrast, chronic glucocorticoid exposure ending e19 or e20 resulted in marked increases in both PNMT and E in adrenal, heart and head tissues. The elevation of E in all three tissues was unaffected by maternal adrenalectomy, indicating enhanced fetal E synthesis. In the absence of exogenous glucocorticoid treatment heart PNMT activity peaked on e12, prior to the earliest reported appearance of glucocorticoid receptors. We conclude that expression of PNMT in all three tissues is glucocorticoid independent until the latter part of gestation when it is readily enhanced by glucocorticoids.

Adrenal Glands↗
PubMed2000

Does caffeine confound relationships among adrenergic tone, blood pressure and sleep apnoea?

The purpose of this study was to determine whether caffeine consumption confounds the relationship among adrenergic tone, as measured by urinary norepinephrine (NE), blood pressure (BP) and obstructive sleep apnoea (OSA). Data were analysed using correlation and regression analysis, analysis of covariance and t-tests. Subjects included normotensives and hypertensives with and without OSA: 38 men, 23 women, aged 30-60 y; 100-150% of ideal body weight; without other major illness. Patients were studied using polysomnography, caffeine consumption was assessed, 24-h urinary NE levels were examined and ambulatory BP was recorded. Patients with OSA (N=27) reported significantly greater caffeine consumption than those without OSA (N=34) (295 vs. 103 mg, P=0.010), but caffeine was not significantly correlated with their ambulatory BP. In contrast, NE excretion correlated with caffeine consumption (r=0.24, P=0.041), apnoea severity (r=0.65, P < 0.001) and BP (r=0.34, P < 0.005). Significant OSA-NE and BP-NE relationships remained even after controlling for caffeine consumption. Patients with OSA consumed nearly three times the amount of caffeine as patients without OSA. While caffeine partially explains the increased adrenergic tone in patients with OSA and the relationship between BP and NE, it does not appear to contribute significantly to the relationship between OSA and elevated BP.

Adult↗
PubMed2000

Peripheral blood mononuclear cell-endothelial adhesion in human hypertension following exercise.

OBJECTIVE: To determine the effects of hypertension and exercise on interleukin-6 (IL-6) levels and mononuclear cell adhesion to endothelial cells. DESIGN: Twelve hypertensive and 33 normotensive volunteers were studied prior to and following exhaustive exercise. End points were stimulated IL-6 levels and peripheral blood mononuclear cell (PBMC) CD11a (LFA-1) expression and in vitro PBMC adhesion to human umbilical venous endothelial cells (HUVEC). RESULTS: In response to exercise, all subjects showed a significant increase in lymphocyte CD11a a density and in IL-6 levels (P < 0.001). Compared to normotensives, hypertensives showed significantly greater mean density of CD11a on lymphocytes (P< 0.05) and on monocytes (P < 0.05). In response to exercise, hypertensive subjects showed a twofold greater increase in IL-6 as compared to normotensives (+ 240 pg/ml versus + 123 pg/ml, respectively; P< 0.05). PBMC adhesion to HUVEC was increased in hypertensives but decreased in normotensives following exercise (P< 0.03). CONCLUSION: The findings suggest that exercise leads to increased mononuclear cell adhesion to endothelial cells in patients with hypertension, possibly through cytokine-induced activation of mononuclear cell CD11a. These findings, coupled with prior data indicating increased endothelial activation in hypertension, may be relevant to the increased risk of atherosclerosis in human hypertension.

Adult↗
PubMed1999

Nonselective beta blockade attenuates the recruitment of CD62L(-)T lymphocytes following exercise.

Exercise induces a selective redistribution of CD62L(-) T lymphocytes. This study examined the effects of beta adrenergic receptor blockade on this phenomenon. Twelve healthy men were exercised to exhaustion on a treadmill prior to and following 1 week of treatment with the nonselective beta antagonist propranolol or the beta1 selective antagonist metoprolol. Dynamic exercise resulted in a significant lymphocytosis (p < 0.001). CD8(+)CD62L(-) T cells showed a greater than 3-fold increase in response to exercise (p < 0.001) as compared to CD8(+)CD62L(+) T cells, which showed a more modest increase. Treatment with the nonselective beta antagonist propranolol significantly attenuated the preferential increase of circulating CD8(+)CD62L(-) lymphocytes (p = 0.01) but had no effect on CD8(+)CD62L(+) T cells. Treatment with the beta1 selective antagonist metoprolol did not affect the response of either subset. Our findings replicate a prior study indicating that CD62L expression influences T lymphocyte trafficking in response to exercise and extends those findings by showing that this phenomenon is mediated, in part, via the beta2-adrenergic receptor.

Adrenergic beta-Antagonists↗
PubMed1999

Accelerated risk of hypertensive blood pressure recordings among Alzheimer caregivers.

The purpose of this study was to determine whether the stress of caregiving for the Alzheimer's disease (AD) patient accelerates the likelihood of exceeding hypertensive blood pressure (BP) criteria in periodic longitudinal home assessments. In this cohort study, participants consisted of spousal caregivers of AD patients (n = 144) and demographically equivalent non-caregiving controls (n = 47). Thirty percent of caregivers and 33% of controls were receiving antihypertensive treatment at study entry. Supine systolic and diastolic blood pressure (SBP and DBP) was assessed by semi-automated recordings taken in the home every 6 months for 2 to 6 years. Survival analyses (Cox proportional hazards models) were used to determine whether the hazard for developing hypertension (DBP>140, SBP>90) was greater in caregivers than in controls, and whether increased hazards were related to background characteristics or the extent of caregiving demands. Based on periodic 6-month assessments of BP over 6 years, the hazards of meeting criteria for borderline hypertension were greater for caregivers than for controls (Cox Proportional Hazards, chi2 [1, N = 174] = 4.86, p = 0.03). This difference remained statistically significant (p<0.05) after controlling for age, gender, education, socioeconomic status, body mass index, and use of antihypertensive medications. Increased risk of hypertension was not related to the extent of daily living assistance provided, patient problem behaviors, or caregiver distress. The chronic stress of caring for an AD spouse may have adverse effects on blood pressure; however, the mechanism for this relationship remains unclear.

Aged↗
PubMed1999

Impedance cardiography-derived hemodynamic responses during baroreceptor testing with amyl nitrite and phenylephrine: a validity and reliability study.

Baroreflex (BR) testing with phenylephrine (PE) and amyl nitrite (AN) provided an opportunity to evaluate the ability of impedance cardiography (IC) to track the rapid hemodynamic (HD) changes elicited by these drugs. The AN response was measured after inhalation and the PE response was measured after a bolus injection in 19 subjects on two occasions. High reliability was observed for all of the HD measures. Blood pressure (BP), peripheral resistance (PR), and preejection period (PEP) decreased significantly after administration of AN, whereas heart rate (HR) and cardiac output (Q) increased. BP and total PR increased significantly after administration of PE; HR and Q decreased and PEP did not change significantly. Stroke volume did not change significantly with either drug. The BR slope was reliably elicited with AN and PE. The IC and Finapres BP consistently detected short-term changes in HD responses to AN and PE. The pharmacological interventions demonstrated that IC measures followed the course predicted by the actions of the drugs. Change in PEP and dZ/dt reflected increased contractility. The BR sensitivity was also reproducible.

Adult↗
PubMed1999

Catecholamine storage vesicle protein expression in genetic hypertension.

Chromogranin A expression is heritable in humans, and both plasma chromogranin A concentration and its releasable adrenal and sympathetic neuronal pools are augmented in established essential (hereditary) hypertension. To evaluate chromogranin A further as a simpler or "intermediate phenotype" in the complex trait of hypertension, we studied chromogranin A expression in the spontaneously hypertensive rat (SHR), a rodent model of essential hypertension. Both plasma (p < 0.0001) and adrenal medullary (p = 0.003 to p < 0.0001) chromogranin A were elevated in the SHR, even at the earliest stages (3-4 weeks of age). In the adult adrenal gland, both chromogranin A (p=0.005) and norepinephrine (p=0.011) were increased in the SHR, while dopamine beta-hydroxylase activity was diminished (p < 0.0001). Chromogranin A mRNA expression was also elevated in the SHR adrenal medulla (p = 0.017). Differences in chromogranin A processing were not noted between SHR and Wistar Kyoto control (WKY) rats. In an SHR x WKY genetic intercross, control of the adrenal chromogranin A phenotype by a single major locus was suggested by comparison of phenotypic variance of the F2 vs F1 generations, and by bimodal frequency histogram (3:1 ratio), confirmed by maximum likelihood analysis (chi2 = 74.6, p < 0.000001) in the F2 generation. However, microsatellite alleles at a surrogate locus (Ighe) 12.7 cM from chromogranin A (Chga), on rat chromosome 6, failed to co-segregate with blood pressure in an F2 generation (F = 0.06, p = 0.94). In another rodent model of hereditary hypertension, the genetically hypertensive mouse (BPH/2), adrenal chromogranin A (p=0.018) and norepinephrine (p = 0.004) were actually diminished. We conclude that over-expression of chromogranin A is a variable feature of mammalian genetic hypertension. In one rodent model (the SHR), over-expression of chromogranin A is largely controlled by a single genetic locus, but the chromogranin A locus itself is not directly linked to determination of the blood pressure elevation of the SHR.

Adrenal Medulla↗
PubMed1999

Effect of exercise on cytokines and growth mediators in prepubertal children.

Many of the anabolic effects of exercise are mediated through insulin-like growth factor-I (IGF-I), but in adolescents, brief exercise training leads to reductions, rather than the expected increase, in circulating IGF-I. Certain cytokines--interleukin-(IL) 1beta (IL-1beta), IL-6 (IL-6), and tumor necrosis factor-alpha--are increased by exercise in adults and are known to inhibit IGF-I. To test the hypothesis that these cytokines might play a role in the adaptation to exercise, we measured the acute effects of exercise on selected cytokines and growth factors in 17 healthy 8- to 11-y-old children (4 females). Designed to mimic patterns and intensity of exercise found in the real lives of American children, the exercise protocol consisted of a 1.5-h soccer practice (of which about 40 min constituted of vigorous exercise). Pre- and postexercise urine and saliva samples were obtained in all subjects and both blood and urine in nine subjects. The exercise led to significant increases in circulating tumor necrosis factor-alpha (18 +/- 7%, p < 0.05) and IL-6 (125 +/- 35%, p < 0.01) as well as a significant increase in the antiinflammatory cytokine IL-1 receptor antagonist (33 +/- 10%, p < 0.01). Urine levels of IL-6 were also substantially increased by exercise (440 +/- 137%, p < 0.0001). Circulating levels of IGF-I were reduced to a small but significant degree (-6.4 +/- 3.2%, p < 0.05), although IGF-binding protein-1 (known to inhibit IGF-I) was substantially increased (156 +/- 40%, p < 0.001). Cytokines are systemically increased after relatively brief exercise in healthy children. This increase may alter critical anabolic agents such as IGF-I and its binding proteins.

Adult↗
PubMed1999

Relationship of arousals from sleep to sympathetic nervous system activity and BP in obstructive sleep apnea.

STUDY OBJECTIVE: Obstructive sleep apnea (OSA) patients have a high frequency of arousals. We hypothesized that arousals significantly influence tonic sympathetic nervous system function. DESIGN: We examined the association of 11 variables measuring sympathetic activity, including plasma norepinephrine (NE), urinary NE, and BP measurements, with movement and cortical arousals. PATIENTS: Sixty-seven subjects with various degrees of hypertension and OSA were evaluated. All patients were free from antihypertensive medications. RESULTS: The age (range, 35 to 60 years), weight (range, 100 to 150% of ideal body weight), and diet of the subjects were similar. The movement arousal index was correlated with daytime baseline plasma NE (BNE), daytime urine NE, mean daytime diastolic BP, and systolic BP during rapid eye movement sleep (r = 0.39 to 0.53; p < or = 0.002). Cortical arousals did not correlate with any of the variables. A multiple regression procedure was performed to examine how well movement arousals predicted those variables with significant correlations. The respiratory disturbance index (RDI) and nighttime pulse oxyhemoglobin saturation were included in the regression equation due to their close association with movement arousals. Movement arousals independently predicted BNE (t [48] = 2.06; p < 0.05). No other variable independently predicted any of the measurements of sympathetic activity. CONCLUSIONS: These findings suggest that movement arousals may influence daytime sympathetic tone independently of RDI and nighttime saturation.

Adult↗
PubMed1999

Sympathetic and respiratory responses to hypoxia in essential hypertension.

An increased sympathetic nervous response to hypoxia and reduced beta-adrenergic receptor function have been reported in hypertension. This study examines the relationship between hypoxia and beta-adrenergic receptor function in sixteen normotensive and eight hypertensive subjects. We measured the average arterial oxygen saturation and the end tidal carbon dioxide partial pressure in hypertensive and normotensive groups under normoxia and mild isocapnic hypoxia (15% O2, 85% N2). The ratio of isoproterenol-stimulated cAMP to basal cAMP on lymphocytes was measured in the two groups under normoxia. We also measured plasma norepinephrine levels and calculated the "Chronotropic 25 Dose" of isoproterenol in the two groups under normoxia and hypoxia. Hypertensives had higher plasma norepinephrine levels for either breathing condition (F=7.16, p=0.015). Under hypoxia, hypertensives showed a significant decrease in the average arterial oxygen saturation (F=4.92, p=0.038) and higher "Chronotropic 25 Dose" implying decreased beta-adrenergic receptor sensitivity (F=6.30, p=0.011). These results suggest that hypertensives have a diminished ventilatory response and impaired beta-adrenergic response under hypoxia.

Adrenergic beta-Agonists↗
PubMed1998

Leptin is related to epinephrine levels but not reproductive hormone levels in cycling African-American and Caucasian women.

This study examined the effects of the menstrual cycle and race on plasma leptin levels. Sixty-one healthy African-American and Caucasian women and men (mean age 32 years) were studied twice, approximately six weeks apart, women once during the follicular phase (days 7-10 following menses) and once during the luteal phase (days 7-10 following LH surge) of the menstrual cycle. Consistent with the literature, women showed approximately 4-fold higher leptin levels as compared to men (p<0.001). There were no effects of the menstrual cycle nor race on leptin levels. Leptin levels were correlated with BMI in both women and men respectively, r=0.602, p<0.001 and r=0.338, p<0.05. Leptin levels showed a high degree of test-retest reliability across the 6-week testing interval (r=0.62, p<0.001 for women and r=0.91, p<0.001 for men). In addition, in women, and independent of BMI, leptin was negatively correlated with plasma epinephrine levels (r=-0.38, p=0.01). No such relationship was observed in men. The findings indicate that in women leptin levels are not associated with cyclic changes in estrogen or progesterone but may be associated with catecholamine levels.

Adult↗
PubMed1998

Mechanism of cardiovascular actions of the chromogranin A fragment catestatin in vivo.

Catestatin (bovine chromogranin A(344-364); RSMRLSFRARGYGFRGPGLQL), reduces catecholamine secretion from chromaffin cells in vitro. We investigated the effects of this peptide on catecholamine release and blood pressure in vivo. Intravenous catestatin reduced pressor responses to activation of sympathetic outflow by electrical stimulation in rats, and the catestatin effect persisted even after adrenergic (alpha plus beta) blockade. Catestatin did not alter plasma norepinephrine levels, but increased plasma epinephrine 11-fold. Catestatin also blunted pressor responses to exogenous neuropeptide Y agonists. A control peptide (chromogranin A(141-160)) did not alter pressor or catecholamine responses to electrical stimulation. Pretreatment with a histamine H1 receptor antagonist blocked both the vasodepressor response to catestatin and the elevation in plasma epinephrine. Catestatin elevated endogenous circulating histamine 21-fold, and exogenous histamine mimicked both the epinephrine elevation and the vasodepressor actions of catestatin. We conclude that catestatin is a potent vasodilator in vivo whose actions appear to be mediated, at least in part, by histamine release and action at H1 receptors.

Adrenergic Antagonists↗
PubMed1997

Sources of human urinary epinephrine.

The kidney is a likely source for some urinary epinephrine (E) since adrenalectomized animals and humans continue to excrete urinary E and the human kidney contains E synthesizing enzymes. We studied subjects during an intravenous infusion of 3H-E to determine the fraction of urinary E derived from the kidney. Eight normal subjects (CON) and 5 older, heavier hypertensives (OHH) ate a light breakfast along with ascorbic acid supplementation and had intravenous and arterial lines placed. They received an infusion of 3H-E and had an oral water load. During the final hour of 3H-E infusion, urine and arterial blood samples were collected for 3H-E and E levels. After the 3H-E infusion was abruptly discontinued, arterial blood samples were collected to measure 3H-E kinetics. The total body clearance of 3H-E was about 2,500 ml/min from plasma and clearance of 3H-E to urine was about 170 ml/min. CON had plasma E levels of 43 +/- 4 pg/ml. Their predicted rate of clearance of E from plasma to urine of 7,471 +/- 865 pg/min was less than (P = 0.018) the actual urinary E excretion of 15,037 +/- 2,625 pg/min. Thus, 43 +/- 9% of urinary E in CON was apparently derived from renal sources and not filtered from blood. Among OHH 85 +/- 4% of urinary E was derived from the kidney, significantly (P < 0.01) different from CON. The OHH also produced much more urinary E than predicted from plasma 3H-E clearance into urine (P = 0.03). A major fraction of urinary E is not filtered from the blood stream but is apparently derived from kidney. A small fraction of urinary E may be derived from E stored in nerve endings along with norepinephrine, but this probably represents less than 2% of urinary E. Renal cleavage of E sulfate into E may be another potential source of urinary E. Some, and perhaps most, urinary E not filtered from the bloodstream is derived from renal N-methylation of norepinephrine as the human kidney has two enzymes capable of converting norepinephrine to E. In conclusion, a major portion of urinary E is derived from the kidney and not filtered from the bloodstream. This is an important factor in the interpretation of urine E levels. Renal E could alter renal blood flow, electrolyte reabsorption, and renin release prior to excretion into urine.

Adult↗
PubMed1997

Sleep apnea, norepinephrine-release rate, and daytime hypertension.

Patients with obstructive sleep apnea (OSA) are often hypertensive, and both apneics and hypertensives are reported to have increased sympathetic nerve activity. We measured plasma norepinephrine (NE) levels, clearance, and release rate among 65 subjects who breathed room air, a hypoxic gas mixture, and the hypoxic mixture combined with intermittent breath holding. Apneics' plasma NE across all three breathing conditions was 307 pg/ml compared with the non-apneics' level of 248 pg/ml (p = 0.017). NE clearance increased from 3.2 l/minute to 3.9 l/minute when subjects breathed a hypoxic gas mixture (p < 0.001). NE clearance was similar among normal controls, apneics, and hypertensives. The rate at which NE was released from sympathetic nerves into the bloodstream was higher among hypertensives but not among apneics while subjects breathed room air. Hypoxia increased the NE-release rate from 892 ng/minute to 1,042 ng/minute (p < 0.001) and increased the NE-release rate more among apneics than non-apneics (p < 0.001). The NE-release rate response to hypoxia and breath holding differed between hypertensives and normotensives (p < 0.001) and between apneics and non-apneics (p < 0.001). Normotensive apneics had the largest increase in NE release during hypoxia. Like other investigators, we found that plasma NE levels were increased among apneics. Calculation of NE-release rate and correction for blood pressure status revealed a more complex situation. Apneics breathing room air had a normal NE-release rate; any increase in sympathetic neuronal NE release could be attributed to apneics who were also hypertensive. However, apneics had a greater NE response to hypoxia. These results suggest that apneics are susceptible to transient increases in sympathetic nervous activity and that hypertensive apneics maintain increased sympathetic nervous release of NE in the daytime.

Adult↗