Spectral changes in skin blood flow during pressure manipulations or sympathetic stimulation.

Skin blood flow is commonly determined by laser Doppler flowmetry (LDF). It has been suggested that pathophysiological conditions can be assessed by analysis of specific frequency domains of the LDF signals. We tested whether physiological stimuli that activate myogenic and neurogenic mechanisms would affect relevant portions of the laser Doppler spectrum. LDF sensors were placed on the right forearm of 14 healthy volunteers for myogenic (six females) and 13 for neurogenic challenge (five females). Myogenic responses were tested by positioning the arm ∼50° above/below heart level. Neurogenic responses were tested by immersing the left hand into an ice slurry with and without topical application of local anaesthetic. Short-time Fourier analyses were computed over the range of 0.06 to 0.15 Hz for myogenic and 0.02 to 0.06 Hz for neurogenic. No significant differences in spectral density were observed (P = 0.40) in the myogenic range with arm above (7 ± 54 × 10-4 dB) and below heart (7 ± 14 × 10-4 dB). Neurogenic spectral density showed no significant increase from baseline to cold pressor test (0.0017 ± 0.0013 and 0.0038 ± 0.0039 dB; P = 0.087, effect size 0.47). After application of anaesthetic, neurogenic spectral density was unchanged between the baseline and cold pressor test (0.0014 ± 0.0025 and 0.0006 ± 0.0005 dB; P = 0.173). These results suggest that changes in the myogenic and neurogenic spectral density of LDF signals did not fully reflect the skin vascular function activated by pressure manipulation and sympathetic stimulation. Therefore, LDF myogenic and neurogenic spectral density data should be interpreted with caution.

Reduction in peripheral arterial stiffness after reactive hyperemia is dependent on increases in blood flow.

The acute reduction in peripheral arterial stiffness during reactive hyperemia is assumed to be flow-mediated; however, the mechanism remains unproven. We hypothesized that restricting the blood flow increase during reactive hyperemia would abolish the reduction in peripheral arterial stiffness. Fourteen healthy young adults (5 females, 25 ± 5 years, mean ± SD) underwent reactive hyperemia with a rapid-release cuff on the upper arm inflated to 220 mmHg for 5 min: once with unrestricted blood flow and once with restricted blood flow by manually applying pressure to the brachial artery. Brachial-radial pulse wave velocity (PWV) was measured with tonometers over brachial and radial arteries before cuff inflation and at 5, 15, and 30 min after release. Brachial blood flow was monitored with Doppler ultrasound. Baseline brachial-radial PWV was similar between conditions (10.3 ± 1.8 vs. 10.7 ± 1.7 m/s). With unrestricted flow, PWV decreased 5 min post-reactive hyperemia (8.6 ± 1.1 m/s; p < 0.05) and returned near baseline at 15 and 30 min post (p < 0.05). With restricted flow, PWV did not change (p > 0.05) post-reactive hyperemia. Reactive hyperemia acutely reduced peripheral arterial stiffness, but not when brachial artery blood flow increase was restricted. This suggests that the reduction in peripheral arterial stiffness during reactive hyperemia depends on increased blood flow.

The effect of aging on carotid artery wall mechanics during maximal resistance exercise.

INTRODUCTION: Age-related stiffening of the large elastic arteries (e.g., common carotid artery [CCA]) may impair wall dynamics (i.e., strain) and amplify transmission of pulsatile blood flow into the brain with large increases in pressure that occur during maximal resistance exercise (RE). The purpose of this study was to compare CCA arterial wall dynamics, central hemodynamics, and cerebral blood velocity responses during maximal RE between young and older adults. METHODS: Thirty-one young (YA; 26 ± 5 yrs; 23.8 ± 3.3 kg/m2) and 25 older adults (OA; 60 ± 6 yrs; 30.0 ± 5.5 kg/m2) performed a unilateral maximal isokinetic knee flexion/extension exercise protocol (i.e., maximal RE). All measures were recorded at baseline and during the last 10 s of maximal RE. Common carotid artery strain, CCA strain time to peak, and CCA strain rate (i.e., variables of arterial wall dynamics) were analyzed using 2D speckle tracking software from circumferential ultrasound images. Transcranial Doppler was used to measure right middle cerebral artery (MCA) blood velocity. Non-invasive arterial blood pressure measurements were obtained using finger photoplethysmography. RESULTS: Older adults had greater reductions in CCA strain time to peak from baseline to maximal RE (345 ± 39 to 242 ± 52 ms) than YA (308 ± 35 to 247 ± 42 ms; interaction effect, p < 0.01). MCA velocity was similar between YA and OA during maximal RE (p = 0.48), despite a greater arterial pressor response in OA (p < 0.01). CONCLUSION: These data suggest cerebral blood velocity responds similarly during maximal RE among OA compared to YA, despite subtle age-related differences in the pressor and extracranial vascular response during maximal RE.

Breast cancer survivors with preserved or rescued cardiorespiratory fitness have similar cardiac, pulmonary and muscle function compared to controls.

Breast cancer survivors (BCS) have a high prevalence of cardiovascular disease and low cardiorespiratory fitness (CRF). CRF is an important predictor of survival in BCS. However, the physiological factors that contribute to low CRF in BCS have not been completely elucidated. To assess differences in physiological factors (cardiac, pulmonary, muscle function) related to CRF between BCS and controls. Twenty-three BCS and 23 age-body mass index (BMI) matched controls underwent a peak cycling exercise test to determine CRF, with physiological factors measured at resting and at peak exercise. Cardiac hemodynamics (stroke volume [SV], SVindex, heart rate [HR], cardiac output [Formula: see text], and [Formula: see text]index) were evaluated using ultrasonography. Pulmonary function was evaluated using the oxygen uptake efficiency slope (OUES), ventilation to carbon dioxide production slope [Formula: see text] and breathing reserve at peak exercise (BR). Muscle oxygenation variables (oxygenated [HbO2] deoxygenated [HHb] and total hemoglobin [Hb], and tissue oxygenation index [TSI]) were measured with near-infrared spectroscopy (NIRS). Both groups had similar CRF and similarly increased all hemodynamic variables (HR, SV, SVindex, [Formula: see text] and [Formula: see text]index) at peak exercise compared to resting (p < 0.001). BCS had higher overall HR and lower SVindex (group effect, p < 0.05). BCS had similar OUES, [Formula: see text] and BR compared to the controls. Both groups decreased TSI, and increased Hb and HHb similarly at peak exercise compared to resting (p < 0.001). Our data suggest BCS do not exhibit differences in cardiac, pulmonary, or muscle function at peak exercise compared to controls, when both groups have similar CRF and physical activity.

Reactive hyperaemia augments local heat-induced skin hyperaemia.

NEW FINDINGS: What is the central question of this study? It is valuable to be able to monitor disease- or treatment-related changes in the microcirculation. Laser Doppler flowmetry with local heating allows non-invasive monitoring of the skin microcirculation and its ability to vasodilate. Does reactive hyperaemia augment the increase in skin blood flow elicited by local heating? What is the main finding and its importance? The addition of reactive hyperaemia to local heating results in greater vasodilatation than heating alone. Thus, reactive hyperaemia can augment local heat-induced hyperaemia in the skin. ABSTRACT: The skin circulation has been proposed as a model of generalized microvascular function that could be monitored non-invasively using laser Doppler flowmetry (LDF). The response to heat hyperaemia (HH) is commonly used to monitor disease- or treatment-related changes in microvascular function. We hypothesized that reactive hyperaemia would augment the increase in skin blood flow elicited by local heating. Fourteen healthy young adults were subjected to three different conditions: reactive hyperaemia (RH; skin temperature controlled at 33°C), heat hyperaemia (HH; 42°C held for 40 min) and HH+RH. Two Peltier-controlled thermomodules with LDF probes were placed on the right forearm to monitor skin blood flow continuously. A cuff was placed on the right upper arm to elicit RH by inflation to 220 mmHg for 5 min. This procedure was performed with the skin temperature at 33°C and again after 40 min of local heating to 42°C. Beat-by-beat mean arterial pressure (MAP) obtained by a photoplethysmographic sensor on the middle finger of the left hand allowed calculation of cutaneous vascular conductance (CVC) as LDF/MAP. Both HH and RH increased LDF (P < 0.0001 and P < 0.0001, respectively) and CVC (P = 0.0001 and P < 0.0001, respectively) above baseline values. The LDF and CVC values were significantly higher during HH+RH when compared with RH or HH alone (P < 0.0001). In summary, HH+RH resulted in greater vasodilatation when compared with HH or RH alone. These results indicate that RH can augment local heat-induced hyperaemia in the skin.

Physical activity is associated with lower pulsatile stress but not carotid stiffness in children.

The cardiovascular disease (CVD) process may begin early in life when accompanied by atherosclerotic risk factors. CVD risk factors in children are associated with stiffening of the large elastic arteries, a reflection of subclinical atherosclerosis. Physical activity is a preventative lifestyle strategy that may benefit arterial stiffness by attenuating the hemodynamic stress on the artery wall. This study examined the relations between physical activity, carotid pulsatile stress, and carotid stiffness in children. One hundred and forty children (9-11 yrs; 50.0% male, 57.9% African-American, 42.10% Caucasian, body mass index (BMI) 20.1 ± 4.7 kg/m2) participated in this study. Physical activity counts were measured using a wrist-worn accelerometer and averaged over 7 days. Carotid artery ß-stiffness and pulse pressure (calibrated to brachial mean and diastolic pressure) were assessed as via ultrasound and tonometry, respectively. Pulsatile stress was calculated as the product of carotid pulse pressure and heart rate. Physical activity counts were correlated with pulsatile stress (r = -0.27), and BMI (r = -0.23), but were unrelated to carotid stiffness. In multivariate models, associations between physical activity counts and pulsatile stress remained (B = -1.3 [95%CI, -2.4, -0.2], ß = -0.20, p < 0.05) after covariate adjustment for age, race, sex, pubertal stage, and BMI. Carotid pulsatile stress was related to regional carotid stiffness (r = 0.45, p < 0.05). These data suggest that higher levels of physical activity at young age are associated with lower hemodynamic stress in the carotid artery. Findings are discussed in the context of an inverse relationship between hemodynamic pulsatile stress and carotid stiffness in children.

Oral vitamin C restores endothelial function during acute inflammation in young and older adults.

Oxidative stress has been linked to reductions in vascular function during acute inflammation in young adults; however, the effect of acute inflammation on vascular function with aging is inconclusive. The aim of this study was to determine if oral antioxidant administration eliminates vascular dysfunction during acute inflammation in young and older adults. Brachial flow-mediated dilation (FMD) and carotid-femoral pulse wave velocity (PWV) were measured in nine young (3 male, 24 ± 4 yrs, 26.2 ± 4.9 kg/m2 ) and 16 older (13 male, 64 ± 5 yrs, 25.8 ± 3.2 kg/m2 ) adults before and 2-h after oral consumption of 2 g of vitamin C. The vitamin C protocol was completed at rest and 24 h after acute inflammation was induced via the typhoid vaccine. Venous blood samples were taken to measure markers of inflammation and vitamin C. Both interleukin-6 (Δ+0.7 ± 1.8 pg/ml) and C-reactive protein (Δ+1.9 ± 3.1 mg/L) were increased at 24 h following the vaccine (p < 0.01). There was no change in FMD or PWV following vitamin C administration at rest (p > 0.05). FMD was lower in all groups during acute inflammation (Δ-1.4 ± 1.9%, p < 0.01), with no changes in PWV (Δ-0.0 ± 0.9 m/s, p > 0.05). Vitamin C restored FMD back to initial values in young and older adults during acute inflammation (Δ+1.0 ± 1.8%, p < 0.01) with no change in inflammatory markers or PWV (p > 0.05). In conclusion, oral vitamin C restored endothelial function during acute inflammation in young and older adults, with no effect on aortic stiffness. The effect of vitamin C on endothelial function did not appear to be due to reductions in inflammatory markers. The exact mechanisms should be further investigated.

Hepatic, renal and inflammatory biomarkers are positively associated with blood pressure changes in healthy pregnant women: a prospective cohort.

This article evaluates the association of hepatic, renal, and inflammatory biomarkers with changes in systolic (SBP) and diastolic (DBP) blood pressure (BP) during healthy pregnancies.A prospective cohort study with 225 healthy pregnant women was conducted in Rio de Janeiro, Brazil. SBP and DBP were evaluated throughout pregnancy (5th-13th, 20th-26th, and 30th-36th gestational weeks) and were the outcomes. The following biomarkers were measured at the first trimester and analyzed according to tertiles of the sample distribution and were considered the main independent predictors: alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), uric acid (UA), creatinine (Cr), and C-reactive protein (CRP) concentrations. The statistical analysis included 3 stages of modeling with the longitudinal linear mixed-effects procedures: Model 1 was adjusted for gestational age and quadratic gestational age; Model 2 included interactions between the biomarkers and gestational age; and Model 3 was adjusted for self-reported skin color, education, parity, early-pregnancy body mass index (BMI) (under/normal <25; overweight/obese ≥25 kg/m), smoking habit, and leisure-time physical activity. Additional models were performed for CRP and UA with the inclusion of interaction terms between the biomarkers and BMI.Women classified in the third tertile of the ALP (≥61.1 U/L; ßSBP = 3.474; 95% confidence interval [CI]: 0.955-5.992; ßDBP = 3.291; 95% CI: 1.098-5.485), ALT (≥14.3 U/L; ßSBP = 2.232; 95% CI: 0.221-4.242; ßDBP = 2.355; 95% CI: 0.721-3.989), and Cr values (≥48.6 µmol/L; ßDBP = 1.927; 95% CI: 0.347-3.508) presented higher BP levels during pregnancy compared to those in the first and second tertiles. Women in the highest tertile of the ALP concentration distribution presented a lower rate of change in SBP and DBP during pregnancy (interaction term with gestational age ßSBP = -0.004; 95% CI: -0.007 to -0.001; P = 0.02; ßDBP = -0.003; 95% CI: -0.006 to -0.001; P = 0.01). Higher UA concentrations were associated with higher SBP levels only in overweight/obese women (ß = 3.878; 95% CI: 0.687-7.068), whereas higher CRP concentrations (≥2.6 mg/L) were associated with higher DBP in under/normal weight women (ß =2.252; 95% CI: 0.267-4.236).ALP, ALT, and Cr concentrations were positively associated with BP levels, whereas ALP was associated with a lower rate of change in BP. The associations of UA and CRP with BP differ according to the early-pregnancy BMI.

Does bromocriptine play a role in decreasing oxidative stress for early weaned programmed obesity?

AIMS: Studies have demonstrated that early weaning can promote metabolic syndrome during adulthood and that obesity increases oxidative stress. Thus, we aimed to evaluate redox status in a pharmacological early weaning rodent model programmed for metabolic syndrome at adulthood. MAIN METHODS: Lactating dams were randomly assigned into 2 groups: the early weaning group (BRO), which was treated intraperitoneally with bromocriptine (1 mg/day) to inhibit prolactin secretion for the last 3 days of lactation, and the control group (C), which received the BRO diluent for the same time period. The offspring were killed at 90 (PN90) and 180 (PN180) days after birth. KEY FINDINGS: Early weaning induced greater visceral adiposity and dyslipidemia. At PN90, the BRO offspring showed glucose intolerance with normoinsulinemia and increased plasma and liver superoxide dismutase, and liver glutathione peroxidase activities, which reduced the liver malondialdehyde but not the increased plasma malondialdehyde levels. However, the BRO offspring showed insulin resistance at PN180 and increased plasma glutathione peroxidase, liver superoxide dismutase, and catalase activities. These changes reduced the plasma and liver malondialdehyde levels, which aided in hepatocyte architecture preservation. Additionally, we observed that sirtuin 1 was overexpressed in the BRO group at PN90, but the increased expression was not maintained through PN180, which suggests unfavorable metabolic conditions in the older offspring. SIGNIFICANCE: Despite the observed obesity and glucose homeostasis dysfunction, our data suggest that the early weaning programming induced by bromocriptine can improve the offspring's redox status and may prevent liver damage during adulthood.

Resveratrol attenuates oxidative stress and prevents steatosis and hypertension in obese rats programmed by early weaning.

We hypothesized that resveratrol, a natural phytoalexin found in grapes, can prevent oxidative stress, obesity and its related disturbances in obese rats programmed by early weaning. Lactating Wistar rats were separated into two groups: early weaning (EW) - dams who were wrapped with a bandage to interrupt the lactation in the last 3 days of lactation; control - dams whose pups had free access to milk during all lactation. At the 150th day, EW offspring were randomly subdivided into EW+resveratrol (EW+Res) - resveratrol (30 mg/kg/day); EW+vehicle (EW) - rats that received 0.5% (w/v) aqueous methylcellulose. The control group received vehicle. Rats were treated by gavage daily for 30 days. EW offspring developed hyperphagia, higher body weight, visceral obesity, higher systolic (SBP) and diastolic blood pressure (DBP) (+15% and +20%, respectively; P<.05) and higher serum triglycerides (TG) and low-density lipoprotein but lower high-density lipoprotein (+55%, +33% and -13%, respectively; P<.05). Resveratrol normalized food intake, SBP and DBP and prevented obesity and dyslipidemia in EW+Res. EW rats had higher plasma and liver thiobarbituric-acid-reactive substances (TBARS) and lower plasma superoxide dismutase (SOD) and liver glutathione peroxidase activities (+51%, +18%, -58%, -31%, respectively; P<.05), and resveratrol normalized both plasma and liver TBARS and increased the activity of SOD and catalase in plasma. EW rats presented liver steatosis and higher liver TG, and resveratrol prevented these hepatic alterations. In conclusion, this study demonstrated a potential therapeutic use of resveratrol in preventing obesity and oxidative stress and reducing the risk of hypertension, dyslipidemia and steatosis in adult rats programmed by early weaning.

Neonatal nicotine exposure causes insulin and leptin resistance and inhibits hypothalamic leptin signaling in adult rat offspring.

Maternal nicotine (NIC) exposure during lactation leads to overweight, hyperleptinemia, and hypothyroidism in adult rat offspring. In this model, we analyzed adipocyte morphology, glucose homeostasis (serum insulin and adiponectin; liver and muscle glycogen), serum lipid, and the leptin signaling pathway. After birth, osmotic minipumps were implanted in lactating rats, which were divided into the groups NIC (6 mg/kg per day s.c. for 14 days) and control (C, saline). NIC and C offspring were killed at the age of 180 days. Adult NIC rats showed higher total body fat (+10%, P<0.05), visceral fat mass (+12%, P<0.05), and cross-sectional area of adipocytes (epididymal: +12% and inguinal: +43%, P<0.05). Serum lipid profile showed no alteration except for apolipoprotein AI, which was lower. We detected a lower adiponectin:fat mass ratio (-24%, P<0.05) and higher insulinemia (+56%, P<0.05), insulin resistance index (+43%, P<0.05), leptinemia (+113%, P<0.05), and leptin:adiponectin ratio (+98%, P<0.05) in the adult NIC group. These rats presented lower hypothalamic contents of the proteins of the leptin signaling pathway (leptin receptor (OB-R): -61%, janus tyrosine kinase 2: -41%, and p-signal transducer and activator of transcription 3: -56%, P<0.05), but higher suppressor of cytokine signaling 3 (+81%, P<0.05). Therefore, NIC exposure only during lactation programs rats for adipocyte hypertrophy in adult life, as well as for leptin and insulin resistance. Through the effects of NIC, perinatal maternal cigarette smoking may be responsible for the future development of some components of the metabolic syndrome in the offspring.