GsMTx-4 normalizes the exercise pressor reflex evoked by intermittent muscle contraction in early stage type 1 diabetic rats.

Emerging evidence suggests the exercise pressor reflex is exaggerated in early stage type 1 diabetes mellitus (T1DM). Piezo channels may play a role in this exaggeration, as blocking these channels attenuates the exaggerated pressor response to tendon stretch in T1DM rats. However, tendon stretch constitutes a different mechanical and physiological stimuli than that occurring during muscle contraction. Therefore, the purpose of this study was to determine the contribution of Piezo channels in evoking the pressor reflex during an intermittent muscle contraction in T1DM. In unanesthetized decerebrate rats, we compared the pressor and cardioaccelerator responses to intermittent muscle contraction before and after locally injecting grammostola spatulata mechanotoxin 4 (GsMTx-4, 0.25 µM) into the hindlimb vasculature. Although GsMTx-4 has a high potency for Piezo channels, it has also been suggested to block transient receptor potential cation (TRPC) channels. We, therefore, performed additional experiments to control for this possibility by also injecting SKF 96365 (10 µM), a TRPC channel blocker. We found that local injection of GsMTx-4, but not SKF 96365, attenuated the exaggerated peak pressor (ΔMAP before: 33 ± 3 mmHg, after: 22 ± 3 mmHg, P = 0.007) and pressor index (ΔBPi before: 668 ± 91 mmHg·s, after: 418 ± 81 mmHg·s, P = 0.021) response in streptozotocin (STZ) rats (n = 8). GsMTx-4 attenuated the exaggerated early onset pressor and the pressor response over time, which eliminated peak differences as well as those over time between T1DM and healthy controls. These data suggest that Piezo channels are an effective target to normalize the exercise pressor reflex in T1DM.NEW & NOTEWORTHY This is the first study to demonstrate that blocking Piezo channels is effective in ameliorating the exaggerated exercise pressor reflex evoked by intermittent muscle contraction, commonly occurring during physical activity, in T1DM. Thus, these findings suggest Piezo channels may serve as an effective therapeutic target to reduce the acute and prolonged cardiovascular strain that may occur during dynamic exercise in T1DM.

Global effects of land use on local terrestrial biodiversity.

Human activities, especially conversion and degradation of habitats, are causing global biodiversity declines. How local ecological assemblages are responding is less clear--a concern given their importance for many ecosystem functions and services. We analysed a terrestrial assemblage database of unprecedented geographic and taxonomic coverage to quantify local biodiversity responses to land use and related changes. Here we show that in the worst-affected habitats, these pressures reduce within-sample species richness by an average of 76.5%, total abundance by 39.5% and rarefaction-based richness by 40.3%. We estimate that, globally, these pressures have already slightly reduced average within-sample richness (by 13.6%), total abundance (10.7%) and rarefaction-based richness (8.1%), with changes showing marked spatial variation. Rapid further losses are predicted under a business-as-usual land-use scenario; within-sample richness is projected to fall by a further 3.4% globally by 2100, with losses concentrated in biodiverse but economically poor countries. Strong mitigation can deliver much more positive biodiversity changes (up to a 1.9% average increase) that are less strongly related to countries' socioeconomic status.

Effects of type 1 diabetes on reflexive cardiovascular responses to intermittent muscle contraction.

Studies have shown that early-stage type 1 diabetes mellitus (T1DM) leads to an exaggerated reflex pressor response to both static muscle contraction and tendon stretch. However, whether similar responses are present during dynamic exercise (i.e., intermittent contraction) is not known. Therefore, the purpose of this study was to determine whether T1DM leads to an exaggerated reflex pressor response to intermittent muscle contraction. We measured the exercise pressor reflex in unanesthetized, decerebrated T1DM (50 mg/kg streptozotocin; STZ) and healthy control (CTL) Sprague-Dawley rats by intermittently contracting the hindlimb muscles for 30 s while measuring mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and heart rate (HR). Intermittently contracting the hindlimb muscles evoked exaggerated mean RSNA (STZ: Δ109 ± 21%, n = 4 rats; CTL: Δ61 ± 8%, n = 5 rats, P < 0.05), peak MAP (STZ: Δ32 ± 2 mmHg, n = 9 rats; CTL: Δ12 ± 2 mmHg, n = 6 rats, P < 0.05), blood pressure index (STZ: Δ625 ± 60 mmHg/s, n = 9 rats; CTL: Δ241 ± 46 mmHg/s, n = 6 rats, P < 0.05), and HR (STZ: Δ24 ± 3 beats/min, n = 9 rats; CTL: Δ9 ± 3 beats/min, n = 6 rats, P < 0.05) responses to similar developed tensions (P > 0.05) in T1DM compared with CTL rats. T1DM rats also exhibited exaggerated early-onset sympathetic (onset: 1 s) and pressor (onset: 5 s) responses. These data show that early-stage T1DM leads to an exaggerated pressor reflex evoked by intermittent muscle contraction. The early onset and greater blood pressure index suggest that cardiovascular strain during dynamic exercise may be significantly higher in individuals with T1DM.NEW & NOTEWORTHY This is the first study to provide evidence that early-stage type 1 diabetes mellitus (T1DM) leads to an exaggerated exercise pressor reflex evoked by intermittent muscle contraction, resulting in substantially higher cardiovascular strain. These findings are significant as they indicate that interventions targeting the exercise pressor reflex may work to alleviate the increased cardiovascular strain and overall burden during exercise in T1DM.

Biomarkers panels can predict fatigue, depression and pain in persons living with HIV: A pilot study.

BACKGROUND: Persons living with HIV experience high symptom burden that can negatively impact medication adherence, work productivity, and quality of life. Symptoms are highly subjective, which can lead to under- or improper treatment. The purpose of this exploratory study was to examine relationships between circulating biomarkers representative of inflammatory, coagulation, and vascular function pathways and prevalent HIV symptoms. SETTING AND SAMPLE: Adults >18 years who were diagnosed with HIV and spoke English for this cross-sectional study were recruited from community clinics and organizations. METHODS: Symptom burden was measured with the HIV Symptom Index; depression with the Patient Health Questionnaire. Human multiplex kits were used to determine serum concentrations of select biomarkers representing inflammatory, coagulation, and vascular function pathways. The biomarkers were included as features in machine learning models to determine which biomarkers predicted the most prevalent HIV symptoms (fatigue and muscle/joint pain) and the symptom of depression. RESULTS: Participants (N = 32) were representative of the local population of people with HIV, being mostly Black (54.4%) and male (60.6%). Depression was predicted by age, gender, glucose, hemoglobin A1c, and inflammation. Muscle/joint pain was predicted by adiponectin, C-reactive protein, and serum amyloid A (SAA). Fatigue was predicted by adiponectin, SAA, and soluble interleukin-1 receptor type II (sIL-1RII). CONCLUSION: Biomarker clusters can be a tool to monitor symptoms. Adding an objective measure to subjective patient experiences could improve management and monitoring of symptoms. Defining a biomarker cluster for the objective assessment of HIV symptoms warrants further investigation; however, the presence of comorbid conditions needs to be controlled.

Exaggerated cardiovascular responses to muscle contraction and tendon stretch in UCD type-2 diabetes mellitus rats.

Patients with type-2 diabetes mellitus (T2DM) have exaggerated sympathetic activity and blood pressure responses to exercise. However, the underlying mechanisms for these responses, as well as how these responses change throughout disease progression, are not completely understood. For this study, we examined the effect of the progression of T2DM on the exercise pressor reflex, a critical neurocardiovascular mechanism that functions to increase sympathetic activity and blood pressure during exercise. We also aimed to examine the effect of T2DM on reflexive cardiovascular responses to static contraction, as well as those responses to tendon stretch when an exaggerated exercise pressor reflex was present. We evoked the exercise pressor reflex and mechanoreflex by statically contracting the hindlimb muscles and stretching the Achilles tendon, respectively, for 30 s. We then compared pressor and cardioaccelerator responses in unanesthetized, decerebrated University of California Davis (UCD)-T2DM rats at 21 and 31 wk following the onset of T2DM to responses in healthy nondiabetic rats. We found that the pressor response to static contraction was greater in the 31-wk T2DM [change in mean arterial pressure (∆MAP) = 39 ± 5 mmHg] but not in the 21-wk T2DM (∆MAP = 24 ± 5 mmHg) rats compared with nondiabetic rats (∆MAP = 18 ± 2 mmHg; P < 0.05). Similarly, the pressor and the cardioaccelerator responses to tendon stretch were significantly greater in the 31-wk T2DM rats [∆MAP = 69 ± 6 mmHg; change in heart rate (∆HR) = 28 ± 4 beats/min] compared with nondiabetic rats (∆MAP = 14 ± 2 mmHg; ∆HR = 5 ± 3 beats/min; P < 0.05). These findings suggest that the exercise pressor reflex changes as T2DM progresses and that a sensitized mechanoreflex may play a role in exaggerating these cardiovascular responses.NEW & NOTEWORTHY This is the first study to provide evidence that as type-2 diabetes mellitus (T2DM) progresses, the exercise pressor reflex becomes exaggerated, an effect that may be due to a sensitized mechanoreflex. Moreover, these findings provide compelling evidence suggesting that impairments in the reflexive control of circulation contribute to exaggerated blood pressure responses to exercise in T2DM.

Exaggerated mechanoreflex in early-stage type 1 diabetic rats: role of Piezo channels.

Recent findings have shown that muscle contraction evokes an exaggerated pressor response in type 1 diabetes mellitus (T1DM) rats; however, it is not known whether the mechanoreflex, which is commonly stimulated by stretching the Achilles tendon, contributes to this abnormal response. Furthermore, the role of mechano-gated Piezo channels, found on thin-fiber afferent endings, in evoking the mechanoreflex in T1DM is also unknown. Therefore, in male and female streptozotocin (STZ, 50 mg/kg)-induced T1DM and healthy control (CTL) rats, we examined the pressor and cardioaccelerator responses to tendon stretch during the early stage of the disease. To determine the role of Piezo channels, GsMTx-4, a selective Piezo channel inhibitor, was injected into the arterial supply of the hindlimb. At 1 wk after STZ injection in anesthetized, decerebrate rats, we stretched the Achilles tendon for 30 s and measured pressor and cardioaccelerator responses. We then compared pressor and cardioaccelerator responses to tendon stretch before and after GsMTx-4 injection (10 µg/100 ml). We found that the pressor (change in mean arterial pressure) response [41 ± 5 mmHg (n = 15) for STZ and 18 ± 3 mmHg (n = 11) for CTL (P < 0.01)] and cardioaccelerator (change in heart rate) response [18 ± 4 beats/min for STZ (n = 15) and 8 ± 2 beats/min (n = 11) for CTL (P < 0.05)] to tendon stretch were exaggerated in STZ rats. Local injection of GsMTx-4 attenuated the pressor [55 ± 7 mmHg (n = 6) before and 27 ± 9 mmHg (n = 6) after GsMTx-4 (P < 0.01)], but not the cardioaccelerator, response to tendon stretch in STZ rats and had no effect on either response in CTL rats. These data suggest that T1DM exaggerates the mechanoreflex response to tendon stretch and that Piezo channels play a role in this exaggeration.

The additive effect of type 2 diabetes on fibrinogen, von Willebrand factor, tryptophan and threonine in people living with HIV.

Chronic immune activation and ensuing inflammation that accompany HIV infection lead to adverse metabolic consequences and an increased risk of type 2 diabetes (T2D). We examined the additive effects of T2D on circulating biomarkers involved in inflammation, coagulation, and vascular function along with plasma amino acids in people living with HIV (PLWH). This cross-sectional study included PLWH with and without T2D (n = 32 total). Analyses involved a multiplex platform for circulating biomarkers and gas chromatography-vacuum ultraviolet spectroscopy for plasma amino acids. In PLWH and T2D, both fibrinogen (2.0 ± 0.6 vs 1.6 ± 0.4 µg/mL, p = 0.02) and von Willebrand factor (vWF) (40.8 ± 17.2 vs 26.7 ± 13.8 µg/mL, p = 0.02) were increased and tryptophan (47 ± 6 vs 53 ± 8 nmol/mL, p = 0.03) and threonine (102 ± 25 vs 125 ± 33 nmol/mL, p = 0.03) were decreased. Fibrinogen, as a biomarker of inflammation, and vWF, as a biomarker of endothelial dysfunction, are augmented by the combined effects of HIV and T2D and may contribute to the pathogenesis of T2D in PLWH. Chronic immune activation and inflammation compromise the integrity of the intestinal mucosa, which increases mucus production. Tryptophan metabolism is altered by a loss of intestinal membrane integrity and threonine is consumed in the production of mucus. Metabolic competition arising from increased protein synthesis in the setting of chronic inflammation along with the associated loss in intestinal membrane integrity may be a primary mechanism in the pathogenesis of T2D in PLWH and requires further investigation.

Acute flavanol consumption improves the cerebral vasodilatory capacity in college-aged African Americans.

NEW FINDINGS: What is the central question of this study? The purpose was to determine whether acute flavanol consumption improves cerebral vasodilatory capacity during rebreathing-induced hypercapnia in African Americans. What is the main finding and its importance? The reduced cerebral vasodilatory response to hypercapnia in young healthy African Americans was improved acutely following consumption of a flavanol-rich beverage. This may have important clinical implications regarding racial differences in cerebrovascular disease risk and possible interventional approaches to offset this risk. African Americans (AAs) have increased risk for cardiovascular and cerebrovascular disease. African Americans have attenuated cerebral vasodilator capacity during hypercapnia relative to Caucasian Americans (CAs). This study tested the hypothesis, using a placebo-controlled crossover design, that acute flavanol consumption improves the range of change in cerebral vascular conductance [CVCI, (a)] and the maximal CVCI (y0) achieved during rebreathing-induced increases in end-tidal carbon dioxide tension. Fourteen college-aged AAs and 14 CAs participated. Both a and y0 were lower in AAs prior to flavanols (for a, AAs, 46 ± 16 versus CAs, 74 ± 18% CVCI, P < 0.001; and for y0, AAs, 151 ± 18 versus CAs, 176 ± 20% CVCI, P = 0.002); however, these variables were increased after flavanols such that there were no differences between groups (for a, AAs, 64 ± 19 versus CAs, 72 ± 22% CVCI, P = 0.35; and for y0, AAs, 166 ± 22 versus CAs, 176 ± 22% CVCI, P = 0.26). Both a and y0 were also lower in AAs prior to placebo (for a, AAs, 52 ± 19 versus CAs, 76 ± 15% CVCI, P = 0.002; and for y0, AAs, 156 ± 20 versus CAs, 177 ± 21% CVCI, P = 0.015), and these differences remained following placebo (for a, AAs, 52 ± 17 versus CAs, 80 ± 20% CVCI, P < 0.001; and for y0, AAs, 152 ± 18 versus CAs, 181 ± 25% CVCI, P = 0.003). These data suggest that acute flavanol consumption improves cerebral vasodilatory capacity during hypercapnia in AAs.

Attenuated cerebral vasodilatory capacity in response to hypercapnia in college-aged African Americans.

NEW FINDINGS: What is the central question of this study? The main purpose of this investigation is to determine whether there is a difference in cerebral vasodilatory capacity in response to rebreathing-induced hypercapnia between African Americans and Caucasian Americans. What is the main finding and its importance? College-aged African Americans have reduced cerebral vasodilatory capacity during hypercapnia when compared with Caucasian counterparts, a finding that suggests cerebral vascular dysfunction in this population. These findings may contribute to the understanding of the greater prevalence of cerebral vascular disease in this population. African Americans (AAs) have increased risk for cardiovascular, cerebral vascular and metabolic disease, including hypertension, stroke, coronary artery disease, metabolic syndrome and type II diabetes, relative to Caucasian Americans (CAs). While it is accepted that endothelial function is impaired in AAs, less is known regarding their cerebral vasodilatory capacity in response to hypercapnia. We hypothesized that AAs have a reduction in the total range of change in cerebral blood flow velocity (CBFV) measured in the middle cerebral artery and an index of cerebral vascular conductance (CVCI) in response to changes in the partial pressure of end-tidal carbon dioxide (P(ET,CO2)) during rebreathing-induced hypercapnia when compared with CAs. Twenty-one healthy, college-aged AA (10 male) and 21 age- and sex-matched CA (10 male) subjects participated in this study. A four-parameter logistic regression was used for curve fitting the responses of CBFV and CVCI relative to changes in P(ET,CO2). The total ranges of change in CBFV (101 ± 18 versus 69 ± 23%; P < 0.001) and CVCI (83 ± 21 versus 58 ± 21%; P < 0.001) as well as the maximal increase in CBFV (205 ± 24 versus 169 ± 24%; P < 0.001) and CVCI (188 ± 30 versus 154 ± 19%; P < 0.001) were reduced during hypercapnia in AAs relative to CAs despite a similar increase in P(ET,CO2) (change, 15 ± 3 versus 15 ± 3 mmHg; P = 0.65). In conclusion, these data indicate that AAs have attenuated cerebral vascular capacity to respond to hypercapnia when compared with CAs.

A global model of the response of tropical and sub-tropical forest biodiversity to anthropogenic pressures.

Habitat loss and degradation, driven largely by agricultural expansion and intensification, present the greatest immediate threat to biodiversity. Tropical forests harbour among the highest levels of terrestrial species diversity and are likely to experience rapid land-use change in the coming decades. Synthetic analyses of observed responses of species are useful for quantifying how land use affects biodiversity and for predicting outcomes under land-use scenarios. Previous applications of this approach have typically focused on individual taxonomic groups, analysing the average response of the whole community to changes in land use. Here, we incorporate quantitative remotely sensed data about habitats in, to our knowledge, the first worldwide synthetic analysis of how individual species in four major taxonomic groups--invertebrates, 'herptiles' (reptiles and amphibians), mammals and birds--respond to multiple human pressures in tropical and sub-tropical forests. We show significant independent impacts of land use, human vegetation offtake, forest cover and human population density on both occurrence and abundance of species, highlighting the value of analysing multiple explanatory variables simultaneously. Responses differ among the four groups considered, and--within birds and mammals--between habitat specialists and habitat generalists and between narrow-ranged and wide-ranged species.

Cerebral vasoreactivity: impact of heat stress and lower body negative pressure.

OBJECTIVE: Cerebrovascular reactivity represents the capacity of the cerebral circulation to raise blood flow in the face of increased demand, and may be reduced in some clinical and physiological conditions. We tested the hypothesis that the hypercapnia-induced increase in cerebral perfusion is attenuated during heat stress (HS) compared to normothermia (NT), and this response is further reduced during the combined challenges of HS and lower body negative pressure (LBNP). METHODS: Ten healthy individuals (9 men) undertook rebreathing-induced hypercapnia during NT, HS, and HS + 20 mmHg LBNP (HSLBNP), while cerebral perfusion was indexed from middle cerebral artery blood velocity (MCA V mean). Cerebrovascular responses were calculated from the slope of the change in MCA V mean and cerebral vascular conductance (CVCi) relative to the increase in end tidal carbon dioxide ([Formula: see text]) during rebreathing. RESULTS: MCA V mean was similar in HS (55 ± 19 cm s(-1)) and HSLBNP (52 ± 16 cm s(-1)), and both values were reduced relative to NT (66 ± 20 cm s(-1)), yet the rise in MCA V mean per Torr increase in [Formula: see text] during rebreathing was similar in each condition (NT: 2.5 ± 0.6 cm s(-1) Torr(-1); HS: 2.4 ± 0.8 cm s(-1) Torr(-1); HSLBNP: 2.1 ± 1.1 cm s(-1) Torr(-1)). Likewise, the rate of increase in CVCi was not different between conditions (NT: 2.1 ± 0.65 cm s(-1 )mmHg(-1)100 Torr(-1); HS: 2.4 ± 0.8 cm s(-1) mmHg(-1) 100 Torr(-1); HSLBNP: 2.0 ± 1.0 cm s(-1) mmHg(-1) 100 Torr(-1)). INTERPRETATIONS: These data indicate that cerebrovascular reactivity is not compromised during whole-body heat stress alone or when combined with mild orthostatic stress relative to normothermic conditions.

Elevated resting heart rate and reduced orthostatic tolerance in obese humans.

BACKGROUND: Obesity is linked with numerous physiological impairments; however, its impact on orthostatic tolerance (OT) remains unknown. This study tested the hypothesis that OT is reduced in obese individuals, and that reduced heart rate (HR) reserve and impaired cerebral autoregulation contribute to impaired OT. METHODS: Eleven obese (8 females) and 22 non-obese (10 females) individuals were exposed to incremental lower body negative pressure (LBNP) to presyncope while HR, arterial blood pressure, and cerebral perfusion (middle cerebral artery blood velocity; MCA V mean) were measured. OT was quantified with a cumulative stress index (CSI). RESULTS: OT was reduced in obese subjects, and there was an inverse relationship between body mass index (BMI) and OT (R = -0.47). HR was higher at rest and during each level of LBNP completed by all subjects. Similar peak HR (HRpeak) during LBNP between obese and non-obese subjects resulted in obese having a higher %peak HR at rest and at each stage of LBNP compared. Relationships existed for BMI and resting %HRpeak (R = 0.45) and resting %HRpeak and CSI (R = -0.52). Despite lower CSI in obese, MCA V mean and indices of cerebral autoregulation were similar between groups at all time points. CONCLUSIONS: These data suggest that OT is reduced in obese and a higher resting HR, but not impaired regulation of cerebral perfusion, may contribute to this reduction.

Variability in orthostatic tolerance during heat stress: cerebrovascular reactivity to arterial carbon dioxide.

INTRODUCTION: A high degree of interindividual variability exists in the magnitude of heat stress (HS)-induced reductions in orthostatic tolerance relative to normothermia (NT). This variability may be associated with HS-mediated reductions in cerebral perfusion (indexed as middle cerebral artery blood velocity; MCAV(mean)) and altered cerebrovascular regulation. METHODS: We tested the hypothesis that cerebrovascular reactivity to hypocapnia would be positively correlated with differences in tolerance to lower body negative pressure (LBNP) [assessed with a cumulative stress index (CSI)] between HS and NT (CSI(diff)). Subjects (N = 13) underwent LBNP twice (NT and HS) separated by > 72 h to assess CSI. On a third day, cerebrovascular reactivity [changes in cerebral vascular conductance (CVCi) during hyperventilation-induced hypocapnia (indexed by end tidal carbon dioxide; P(ET)CO2)] was assessed during NT, HS, and HS+LBNP (-20 mmHg; HS(LBNP)). RESULTS: Tolerance to LBNP was reduced after a 1.5 +/- 0.1 degrees C increase in internal temperature and a high degree of variability was observed for CSI(diff) (range: 122 to 1826 mmHg x min(-1)). The magnitude of reduction in CVCi during voluntary hyperventilation-induced hypocapnia (-16 +/- 5 Torr) was attenuated during HS and HS(LBNP) VS. NT (NT: -0.20 +/- 0.09 cm x s(-1) x mmHg(-1); HS: -0.12 +/- 0.09 cm x s(-1) x mmHg(-1); HS(LBNP): -0.11 +/- 0.11 cm x s(-1). mmHg(-1)); however, no relationship existed between deltaCVCi/ P(ET)CO2 and CSI(diff) in any condition. CONCLUSIONS: Cerebrovascular reactivity to hyperventilation-induced hypocapnia is attenuated when internal temperature is elevated, perhaps as a protective mechanism to protect against further reductions in the already diminished cerebral perfusion in this thermal state. However, individual differences in these responses do not appear to predict orthostatic tolerance during HS.

Cyclooxygenase products contribute to the exaggerated exercise pressor reflex evoked by static muscle contraction in male UCD-type 2 diabetes mellitus rats.

Cyclooxygenase (COX) products of arachidonic acid metabolism, specifically prostaglandins, play a role in evoking and transmitting the exercise pressor reflex in health and disease. Individuals with type 2 diabetes mellitus (T2DM) have an exaggerated exercise pressor reflex; however, the mechanisms for this exaggerated reflex are not fully understood. We aimed to determine the role played by COX products in the exaggerated exercise pressor reflex in T2DM rats. The exercise pressor reflex was evoked by static muscle contraction in unanesthetized, decerebrate, male, adult University of California Davis (UCD)-T2DM (n = 8) and healthy Sprague-Dawley (n = 8) rats. Changes (Δ) in peak mean arterial pressure (MAP) and heart rate (HR) during muscle contraction were compared before and after intra-arterial injection of indomethacin (1 mg/kg) into the contracting hindlimb. Data are presented as means ± SD. Inhibition of COX activity attenuated the exaggerated peak MAP (Before: Δ32 ± 13 mmHg and After: Δ18 ± 8 mmHg; P = 0.004) and blood pressor index (BPi) (Before: Δ683 ± 324 mmHg·s and After: Δ361 ± 222 mmHg·s; P = 0.006), but not HR (Before: Δ23 ± 8 beats/min and After Δ19 ± 10 beats/min; P = 0.452) responses to muscle contraction in T2DM rats. In healthy rats, COX activity inhibition did not affect MAP, HR, or BPi responses to muscle contraction. Inhibition of COX activity significantly reduced local production of prostaglandin E2 in T2DM and healthy rats. We conclude that peripheral inhibition of COX activity attenuates the pressor response to muscle contraction in T2DM rats, suggesting that COX products partially contribute to the exaggerated exercise pressor reflex in those with T2DM.NEW & NOTEWORTHY We compared the pressor and cardioaccelerator responses to static muscle contraction before and after inhibition of cyclooxygenase (COX) activity within the contracting hindlimb in decerebrate, unanesthetized type 2 diabetic mellitus (T2DM) and healthy rats. The pressor responses to muscle contraction were attenuated after peripheral inhibition of COX activity in T2DM but not in healthy rats. We concluded that COX products partially contribute to the exaggerated pressor reflex in those with T2DM.

Spontaneous baroreflex sensitivity is attenuated in male UCD-type 2 diabetes mellitus rats: A link between metabolic and autonomic dysfunction.

Patients with type 2 diabetes mellitus (T2DM) have impaired arterial baroreflex function, which may be linked to the co-existence of obesity. However, the role of obesity and its related metabolic impairments on baroreflex dysfunction in T2DM is unknown. This study aimed to investigate the role of visceral fat and adiponectin, the most abundant cytokine produced by adipocytes, on baroreflex dysfunction in T2DM rats. Experiments were performed in adult male UCD-T2DM rats assigned to the following experimental groups (n = 6 in each): prediabetic (Pre), diabetes-onset (T0), 4 weeks after onset (T4), and 12 weeks after onset (T12). Age-matched healthy Sprague-Dawley rats were used as controls. Rats were anesthetized and blood pressure was directly measured on a beat-to-beat basis to assess spontaneous baroreflex sensitivity (BRS) using the sequence technique. Dual-energy X-ray absorptiometry (DEXA) was used to assess body composition. Data are presented as mean ± SD. BRS was significantly lower in T2DM rats compared with controls at T0 (T2D: 3.7 ± 3.2 ms/mmHg vs Healthy: 16.1 ± 8.4 ms/mmHg; P = 0.01), but not at T12 (T2D: 13.4 ± 8.1 ms/mmHg vs Healthy: 9.2 ± 6.0 ms/mmHg; P = 0.16). T2DM rats had higher visceral fat mass, adiponectin, and insulin concentrations compared with control rats (all P < 0.01). Changes in adiponectin and insulin concentrations over the measured time-points mirrored one another and were opposite those of the BRS in T2DM rats. These findings demonstrate that obesity-related metabolic impairments may contribute to an attenuated spontaneous BRS in T2DM, suggesting a link between metabolic and autonomic dysfunction.

Effects of meditation compared to music listening on biomarkers in breast cancer survivors with cognitive complaints: secondary outcomes of a pilot randomized control trial.

CONTEXT: We previously reported positive behavioral effects of both daily mantra meditation and classical music listening interventions in breast cancer survivors with cancer related cognitive complaints. OBJECTIVE: The objective of this pilot study was to compare the effects of the meditation intervention to a music listening intervention on biomarkers of inflammation and cellular aging (secondary outcomes) in breast cancer survivors. DESIGN: Randomized control trial, baseline data collection (time 1), post intervention data collection (time 2) SETTING: Community-based, Central Texas PARTICIPANTS: 25 breast cancer survivors (BCS) who were 3 months to 6 years post chemotherapy completion and reported cognitive changes. INTERVENTION(S): Kirtan Kriya meditation (KK) or classical music listening (ML), 8 weeks, 12 min a day MAIN OUTCOME: Telomerase activity [TA], c-reactive protein [CRP], soluble IL-2 receptor alpha [sIL-2Rα], soluble IL-4 receptor [sIL-4R], soluble IL-6 receptor [sIL-6R], soluble tumor necrosis factor receptor II [sTNF-RII], VEGF receptor 2 [sVEGF-R2], and VEGF receptor 3 [sVEGF-R3] RESULTS: Repeated measures analysis of variance models were analyzed from time 1 to time 2 by group for each biomarker. A pattern of greater telomerase activity across time in both groups (F (1,15) = 3.98, p = .06, ω2 = 0.04); significant decreases in sIL-4R across time for both groups (F (1,22) = 6.28, p = .02, ω2 = .003); group*time effect was nominally different but not statistically different for sIL-4R (F(1,22) = 3.82, p = .06, ω2 = .001); and a pattern for a group*time effect with ML group showing higher levels of sVEGF-R3 at time 2 (F (1,20) = 2.59, p = .12, ω2 = .009). No significant effects were found for CRP, sIL-2Rα, sIL-6R, sTNF-RII, or sVEGF-R2.

Exaggerated exercise pressor reflex in male UC Davis type 2 diabetic rats is due to the pathophysiology of the disease and not aging.

Introduction: Studies in humans and animals have found that type 2 diabetes mellitus (T2DM) exaggerates the blood pressure (BP) response to exercise, which increases the risk of adverse cardiovascular events such as heart attack and stroke. T2DM is a chronic disease that, without appropriate management, progresses in severity as individuals grow older. Thus, it is possible that aging may also exaggerate the BP response to exercise. Therefore, the purpose of the current study was to determine the effect of the pathophysiology of T2DM on the exercise pressor reflex independent of aging. Methods: We compared changes in peak pressor (mean arterial pressure; ΔMAP), BP index (ΔBPi), heart rate (ΔHR), and HR index (ΔHRi) responses to static contraction, intermittent contraction, and tendon stretch in UCD-T2DM rats to those of healthy, age-matched Sprague Dawley rats at three different stages of the disease. Results: We found that the ΔMAP, ΔBPi, ΔHR, and ΔHRi responses to static contraction were significantly higher in T2DM rats (ΔMAP: 29 ± 4 mmHg; ΔBPi: 588 ± 51 mmHg•s; ΔHR: 22 ± 5 bpm; ΔHRi: 478 ± 45 bpm•s) compared to controls (ΔMAP: 10 ± 1 mmHg, p < 0.0001; ΔBPi: 121 ± 19 mmHg•s, p < 0.0001; ΔHR: 5 ± 2 bpm, p = 0.01; ΔHRi: 92 ± 19 bpm•s, p < 0.0001) shortly after diabetes onset. Likewise, the ΔMAP, ΔBPi, and ΔHRi to tendon stretch were significantly higher in T2DM rats (ΔMAP: 33 ± 7 mmHg; ΔBPi: 697 ± 70 mmHg•s; ΔHRi: 496 ± 51 bpm•s) compared to controls (ΔMAP: 12 ± 5 mmHg, p = 0.002; ΔBPi: 186 ± 30 mmHg•s, p < 0.0001; ΔHRi: 144 ± 33 bpm•s, p < 0.0001) shortly after diabetes onset. The ΔBPi and ΔHRi, but not ΔMAP, to intermittent contraction was significantly higher in T2DM rats (ΔBPi: 543 ± 42 mmHg•s; ΔHRi: 453 ± 53 bpm•s) compared to controls (ΔBPi: 140 ± 16 mmHg•s, p < 0.0001; ΔHRi: 108 ± 22 bpm•s, p = 0.0002) shortly after diabetes onset. Discussion: Our findings suggest that the exaggerated exercise pressor reflex and mechanoreflex seen in T2DM are due to the pathophysiology of the disease and not aging.

Endothelial ischemia-reperfusion injury in humans: association with age and habitual exercise.

Advancing age is a major risk factor for coronary artery disease. Endothelial dysfunction accompanied by increased oxidative stress and inflammation with aging may predispose older arteries to greater ischemia-reperfusion (I/R) injury. Because coronary artery ischemia cannot be induced safely, the effects of age and habitual endurance exercise on endothelial I/R injury have not been determined in humans. Using the brachial artery as a surrogate model of the coronary arteries, endothelial function, assessed by brachial artery flow-mediated dilation (FMD), was measured before and after 20 min of continuous forearm occlusion in young sedentary (n = 10, 24 ± 2 yr) and middle-aged (n = 9, 48 ± 2 yr) sedentary adults to gain insight into the effects of primary aging on endothelial I/R injury. Young (n = 9, 25 ± 1 yr) and middle-aged endurance-trained (n = 9, 50 ± 2 yr) adults were also studied to determine whether habitual exercise provides protection from I/R injury. Fifteen minutes after ischemic injury, FMD decreased significantly by 37% in young sedentary, 35% in young endurance-trained, 68% in middle-aged sedentary, and 50% in middle-aged endurance-trained subjects. FMD returned to baseline levels within 30 min in young sedentary and endurance-trained subjects but remained depressed in middle-aged sedentary and endurance-trained subjects. Circulating markers of antioxidant capacity and inflammation were not related to FMD. In conclusion, advancing age is associated with a greater magnitude and delayed recovery from endothelial I/R injury in humans. Habitual endurance exercise may provide partial protection to the endothelium against this form of I/R injury with advancing age.

Impact of Menstrual Blood Loss and Oral Contraceptive Use on Oxygen-carrying Capacity.

PURPOSE: The effect of menstrual blood loss on oxygen-carrying capacity remains equivocal. The purpose of this study was to determine the effect of menstrual blood loss on hemoglobin mass in young, healthy women. METHODS: Twenty-one women (age, 23 ± 6 yr; height, 168 ± 7 cm; weight, 66.1 ± 12.6 kg) with regular menstrual cycles, either using (n = 10) or not using oral contraceptives, participated in the study. Hemoglobin mass was assessed using carbon monoxide rebreathing on three separate occasions over the course of one menstrual cycle. RESULTS: Visits for women not using oral contraceptives were performed in the early follicular phase (3 ± 1 d after the onset of menses), late follicular phase (1 ± 1 d after the surge of luteinizing hormone in urine), and luteal phase (9 ± 1 d after the late follicular visit). Visits for women using oral contraceptives were performed in the early follicular phase (3 ± 1 d after the onset of menses), late follicular phase (15 ± 3 d after the onset of menses), and luteal phase (9 ± 2 d after the late follicular visit). Hemoglobin mass was not affected by menstrual cycle phase (early follicular, 618 ± 61; late follicular, 610 ± 65; luteal, 607 ± 68 g; P = 0.52). Interestingly, when normalized to weight, hemoglobin mass was 12% higher in women using oral contraceptives in comparison to nonusers (10.0 ± 1.2 vs 8.9 ± 1.2 g·kg, P < 0.05). CONCLUSION: Menstrual blood loss had no measurable effect on hemoglobin mass in eumenorrheic women. However, oral contraceptive use resulted in a greater oxygen-carrying capacity, potentially leading to a greater maximal oxygen uptake.

A randomized control trial of meditation compared to music listening to improve cognitive function for breast cancer survivors: Feasibility and acceptability.

BACKGROUND: and Purpose: Many breast cancer survivors (BCS) experience persistent cognitive and psychological changes associated with their cancer and/or treatment and that have limited treatment options. Therefore, the purpose of this study was to explore the feasibility and effects of a Kirtan Kriya meditation (KK) intervention on cognitive and psychological symptoms compared to an attention control condition, classical music listening (ML), in BCS. MATERIALS AND METHODS: A randomized control trial design was used. Participants completed eight-week interventions. Cognitive function and psychological symptoms were measured at baseline and post-intervention. Mixed analysis of variance models were examined for all cognitive and psychological outcomes. RESULTS: 27 BCS completed the study. Intervention adherence was 88%. Both groups improved in perceived cognitive impairments, cognition related quality of life, verbal memory, and verbal fluency (p's < 0.01). There were no significant group by time effects for cognitive and psychological outcomes, except stress. The ML group reported lower stress at time 2 (p < 0.05). CONCLUSION: KK and ML are feasible, acceptable, and cost-effective interventions that may be beneficial for survivors' cognition and psychological symptoms. Both interventions were easy to learn, low cost, and required just 12 min/day. Meditation or music listening could offer providers evidence-based suggestions to BCS experiencing cognitive symptoms. CLINICAL TRIALS REGISTRATION NUMBER: NCT03696056.