Acute and chronic stress have been reported to have differing effects on physical activity in rodents, but no study has examined a chronic stress protocol that incorporates stressors often ...experienced by rodents throughout a day. To examine this, the effects of the Unpredictable Chronic Mild Stress (UCMS) protocol on voluntary running wheel activity at multiple time points, and/or in response to acute removal of chronic stress was determined. Twenty male Balb/c mice were given access and accustomed to running wheels for 4 weeks, after which they were randomized into 2 groups; exercise (EX, n = 10) and exercise with chronic stress using a modified UCMS protocol for 7 hours/day (8:00 a.m.-3:00p.m.), 5 days/week for 8 weeks (EXS, n = 10). All mice were given access to running wheels from approximately 3:30 p.m. to 7:30 a.m. during the weekday, however during weekends mice had full-time access to running wheels (a time period of no stress for the EXS group). Daily wheel running distance and time were recorded. The average running distance, running time, and work each weekday was significantly lower in EXS compared to EX mice, however, the largest effect was seen during week one. Voluntary wheel running deceased in all mice with increasing age; the pattern of decline appeared to be similar between groups. During the weekend (when no stress was applied), EXS maintained higher distance compared to EX, as well as higher daily distance, time, and work compared to their weekday values. These results indicate that mild chronic stress reduces total spontaneous wheel running in mice during the first week of the daily stress induction and maintains this reduced level for up to 8 consecutive weeks. However, following five days of UCMS, voluntary running wheel activity rebounds within 2-3 days.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The deterioration in arterial and cardiac function with aging impairs arterial ventricular coupling, an important determinant of cardiovascular performance. However, exercise training improves ...arterial ventricular coupling especially during exercise. This review examines the concept of arterial-ventricular coupling and how age and disease uncouples, but exercise training recouples, the heart and arterial system.
Vaping, or electronic cigarette (ecig) use, is prevalent among pregnant women, although little is known about the effects of perinatal ecig use on cardiovascular health of the progeny (even when ...using nicotine-free e-liquid). Maternal toxicant inhalation may adversely affect vital conduit vessel development. We tested the hypothesis that perinatal exposure to maternal vaping would lead to a dose-dependent dysfunction that would persist into later life of offspring. Pregnant Sprague-Dawley rats were exposed to either nicotine-free (ecig0) or nicotine-containing ecig aerosol (18 mg/mL, ecig18) starting on
and continued until pups were weaned (
). Pups were never directly exposed. Conduit artery function (stiffness and reactivity) and structure were assessed in 3- and 7-mo-old offspring. At 3 mo, pulse wave velocity (PWV) in the ecig0 and ecig18 offspring was significantly higher than controls in both the 20 puffs/day (6.6 ± 2.1 and 4.8 ± 1.3 vs. 3.2 ± 0.7 m/s, respectively,
< 0.05, means ± SD) and in 60 puffs/day exposure cohort (7.5 ± 2.8 and 7.5 ± 2.5 vs. 3.2 ± 0.5 m/s, respectively,
< 0.01). Wire myography revealed (range of 23%-31%) impaired aortic relaxation in all ecig exposure groups (with or without nicotine). Incubation of vessels with TEMPOL or Febuxostat reversed the aortic dysfunction, implicating the involvement of reactive oxygen species. Nearly identical changes and pattern was seen in vascular outcomes of 7-mo-old offspring. The take-home message from this preclinical study is that maternal vaping during pregnancy, with or without nicotine, leads to maladaptations in vascular (aortic) development that persist into adult life of offspring.
We observe a significant alteration in arterial structure and function in adolescent and adult offspring due to developmental exposure to toxicants resulting from perinatal maternal vaping. Taken together with previous work that described lasting dysfunction in cerebral microvasculature in offspring, these data underscore the adverse consequences of maternal exposure to electronic cigarette aerosol in conduit and resistance vessels alike, irrespective of nicotine content.
The metabolic syndrome (MetS) is associated with a threefold increase risk of cardiovascular disease (CVD) mortality partly due to increased arterial stiffening. We compared the effects of aerobic ...exercise training on arterial stiffening/mechanics in MetS subjects without overt CVD or type 2 diabetes. MetS and healthy control (Con) subjects underwent 8 wk of exercise training (ExT; 11 MetS and 11 Con) or remained inactive (11 MetS and 10 Con). The following measures were performed pre- and postintervention: radial pulse wave analysis (applanation tonometry) was used to measure augmentation pressure and index, central pressures, and an estimate of myocardial efficiency; arterial stiffness was assessed from carotid-femoral pulse-wave velocity (cfPWV, applanation tonometry); carotid thickness was assessed from B-mode ultrasound; and peak aerobic capacity (gas exchange) was performed in the seated position. Plasma matrix metalloproteinases (MMP) and CVD risk (Framingham risk score) were also assessed. cfPWV was reduced (P < 0.05) in MetS-ExT subjects (7.9 ± 0.6 to 7.2 ± 0.4 m/s) and Con-ExT (6.6 ± 1.8 to 5.6 ± 1.6 m/s). Exercise training reduced (P < 0.05) central systolic pressure (116 ± 5 to 110 ± 4 mmHg), augmentation pressure (9 ± 1 to 7 ± 1 mmHg), augmentation index (19 ± 3 to 15 ± 4%), and improved myocardial efficiency (155 ± 8 to 168 ± 9), but only in the MetS group. Aerobic capacity increased (P < 0.05) in MetS-ExT (16.6 ± 1.0 to 19.9 ± 1.0) and Con-ExT subjects (23.8 ± 1.6 to 26.3 ± 1.6). MMP-1 and -7 were correlated with cfPWV, and both MMP-1 and -7 were reduced post-ExT in MetS subjects. These findings suggest that some of the pathophysiological changes associated with MetS can be improved after aerobic exercise training, thereby lowering their cardiovascular risk.
Maintenance of adequate tissue perfusion through a dense network of cerebral microvessels is critical for the perseveration of normal brain function. Regulation of the cerebral blood flow has to ...ensure adequate delivery of nutrients and oxygen with moment-to-moment adjustments to avoid both hypo- and hyper-perfusion of the brain tissue. Even mild impairments of cerebral blood flow regulation can have significant implications on brain function. Evidence suggests that chronic stress and depression elicits multifaceted functional impairments to the cerebral microcirculation, which plays a critical role in brain health and the pathogenesis of stress-related cognitive impairment and cerebrovascular events. Identifying the functional and structural changes to the brain that are induced by stress is crucial for achieving a realistic understanding of how related illnesses, which are highly disabling and with a large economic cost, can be managed or reversed. This overview discusses the stress-induced alterations in neurovascular coupling with specific attention to cerebrovascular regulation (endothelial dependent and independent vasomotor function, microvessel density). The pathophysiological consequences of cerebral microvascular dysfunction with stress and depression are explored.
Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland
ABSTRACT
Understanding the performance of the left ...ventricle (LV) requires not only examining the properties of the LV itself, but also investigating the modulating effects of the arterial system on left ventricular performance. The interaction of the LV with the arterial system, termed arterial-ventricular coupling (E A /E LV ), is a central determinant of cardiovascular performance and cardiac energetics. E A /E LV can be indexed by the ratio of effective arterial elastance (E A ; a measure of the net arterial load exerted on the left ventricle) to left ventricular end-systolic elastance (E LV ; a load-independent measure of left ventricular chamber performance). At rest, in healthy individuals, E A /E LV is maintained within a narrow range, which allows the cardiovascular system to optimize energetic efficiency at the expense of mechanical efficacy. During exercise, an acute mismatch between the arterial and ventricular systems occurs, due to a disproportionate increase in E LV (from an average of 4.3 to 13.2, and 4.7 to 15.5 mmHg·ml –1 ·m –2 in men and women, respectively) vs. E A (from an average of 2.3 to 3.2, and 2.3 to 2.9 mmHg·ml –1 ·m –2 in men and women, respectively), to ensure that sufficient cardiac performance is achieved to meet the increased energetic requirements of the body. As a result E A /E LV decreases from an average of 0.58 to 0.34, and 0.52 to 0.27 in men and women, respectively. In this review, we provide an overview of the concept of E A /E LV , and examine the effects of age, hypertension, and heart failure on E A /E LV and its components (E A and E LV ) in men and women. We discuss these effects both at rest and during exercise and highlight the mechanistic insights that can be derived from studying E A /E LV .
left ventricular function; arterial system; exercise; aging; disease
Address for reprint requests and other correspondence: S. S. Najjar, Laboratory of Cardiovascular Science, NIA-NIH, 5th Floor, Harbor Hospital, 3001 S. Hanover St., Baltimore, MD 21225 (e-mail: Najjarsa{at}mail.nih.gov )
Proponents for electronic cigarettes (E-cigs) claim that they are a safe alternative to tobacco-based cigarettes; however, little is known about the long-term effects of exposure to E-cig vapor on ...vascular function. The purpose of this study was to determine the cardiovascular consequences of chronic E-cig exposure. Female mice (C57BL/6 background strain) were randomly assigned to chronic daily exposure to E-cig vapor, standard (3R4F reference) cigarette smoke, or filtered air ( n = 15/group). Respective whole body exposures consisted of four 1-h-exposure time blocks, separated by 30-min intervals of fresh air breaks, resulting in intermittent daily exposure for a total of 4 h/day, 5 days/wk for 8 mo. Noninvasive ultrasonography was used to assess cardiac function and aortic arterial stiffness (AS), measured as pulse wave velocity, at three times points (before, during, and after chronic exposure). Upon completion of the 8-mo exposure, ex vivo wire tension myography and force transduction were used to measure changes in thoracic aortic tension in response to vasoactive-inducing compounds. AS increased 2.5- and 2.8-fold in E-cig- and 3R4F-exposed mice, respectively, compared with air-exposed control mice ( P < 0.05). The maximal aortic relaxation to methacholine was 24% and 33% lower in E-cig- and 3R4F-exposed mice, respectively, than in controls ( P < 0.05). No differences were noted in sodium nitroprusside dilation between the groups. 3R4F exposure altered cardiac function by reducing fractional shortening and ejection fraction after 8 mo ( P < 0.05). A similar, although not statistically significant, tendency was also observed with E-cig exposure ( P < 0.10). Histological and respiratory function data support emphysema-associated changes in 3R4F-exposed, but not E-cig-exposed, mice. Chronic exposure to E-cig vapor accelerates AS, significantly impairs aortic endothelial function, and may lead to impaired cardiac function. The clinical implication from this study is that chronic use of E-cigs, even at relatively low exposure levels, induces cardiovascular dysfunction. NEW & NOTEWORTHY Electronic cigarettes (E-cigs) are marketed as safe, but there has been insufficient long-term exposure to humans to justify these claims. This is the first study to report the long-term in vivo vascular consequences of 8 mo of exposure to E-cig vapor in mice (equivalent to ~25 yr of exposure in humans). We report that E-cig exposure increases arterial stiffness and impairs normal vascular reactivity responses, similar to other risk factors, including cigarette smoking, which contribute to the development of cardiovascular disease.
Vasomotor response is related to the capacity of the vessel to maintain vascular tone within a narrow range. Two main control mechanisms are involved: the autonomic control of the sympathetic neural ...drive (global control) and the endothelial smooth cells capacity to respond to mechanical stress by releasing vasoactive factors (peripheral control). The aim of this study was to evaluate the effects of respiratory muscle training (RMT) on vasomotor response, assessed by flow-mediated dilation (FMD) and heart rate variability, in young healthy females. The hypothesis was that RMT could enhance the balance between sympathetic and parasympathetic neural drive and reduce vessel shear stress. Thus, twenty-four women were randomly assigned to either RMT or SHAM group. Maximal inspiratory mouth pressure and maximum voluntary ventilation were utilized to assess the effectiveness of the RMT program, which consisted of three sessions of isocapnic hyperventilation/ week for eight weeks, (twenty-four training sessions). Heart rate variability assessed autonomic balance, a global factor regulating the vasomotor response. Endothelial function was determined by measuring brachial artery vasodilation normalized by shear rate (%FMD/SR). After RMT, but not SHAM, maximal inspiratory mouth pressure and maximum voluntary ventilation increased significantly (+31% and +16%, respectively). Changes in heart rate variability were negligible in both groups. Only RMT exhibited a significant increase in %FMD/SR (+45%; p<0.05). These data suggest a positive effect of RMT on vasomotor response that may be due to a reduction in arterial shear stress, and not through modulation of sympatho-vagal balance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Electronic cigarettes (e-cigs) are customizable tobacco products that allow users to select e-liquid composition, flavors, and (in some devices) adjust wattage or heat used to generate e-cig aerosol. ...This study compared vascular outcomes in a conducting vessel (thoracic aorta) and a resistance artery (middle cerebral artery, MCA) in C57Bl/6 mice exposed to e-cig aerosol generated from either pure vegetable glycerin (VG) or pure propylene glycol (PG) over 60-min (Study 1), and separately the effect of using 5- vs. 30-watt settings with an exposure of 100-min (Study 2). In Study 1, aortic endothelial-dependent-dilation (EDD) was only impaired with PG- exposure (p < 0.05) compared with air. In the MCA, EDD response was impaired by ∼50% in both VG and PG groups compared with air (p < 0.05). In Study 2, the aortic EDD responses were not different for either 5- or 30-watt exposed groups compared with air controls; however, in the MCA, both 5- and 30-watt groups were impaired by 32% and 55%, respectively, compared with air controls (p < 0.05). These pre-clinical data provide evidence that chronic exposure to aerosol produced by either VG or PG, and regardless of the wattage used, leads to vascular dysfunction at multiple levels within the arterial system. For all exposures, we observed greater impairment of arterial reactivity in a resistance artery (i.e. MCA) compared with the aorta. These data could suggest the smaller arteries may be more sensitive or first to be affected, or that different mechanism(s) for impairment may be involved depending on arterial hierarchy.
•E-cig exposure to either VG or PG alone triggers arterial vascular dysfunction.•E-cig exposure at even very low wattages results in significant vascular impairment compared to air-exposed controls.•E-cig triggers vascular dysfunction at multiple levels within the arterial system.•Resistance arteries have greater dysfunction compared to conducting vessels.
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