Regular brief interruptions to sitting after a high-energy evening meal attenuate glycemic excursions in overweight/obese adults.

BACKGROUND AND AIMS: Modern Western lifestyles are characterized by consumption of approximately 45% of total daily energy intake at the evening meal, followed by prolonged sitting while watching television (TV), which may deleteriously impact glycemic control. After a high-energy evening meal (dinner), we examined whether regular, brief activity bouts during TV commercial breaks could acutely lower postprandial glucose and insulin responses in overweight/obese adults, compared to prolonged uninterrupted sitting. METHODS AND RESULTS: Nine overweight/obese adults (29.7 ± 4.06 kg m-2; aged 32 ± 3 years; 5 male) completed two laboratory-based conditions of three and a half hours: prolonged sitting during TV viewing (SIT); and, prolonged sitting interrupted every 20 min with 3 min of light-intensity body-weight resistance activities (active commercial breaks; ACBs). Venous postprandial glucose and insulin responses to dinner were calculated as positive incremental area under the curve (iAUC) from baseline. Interstitial glucose was measured using a continuous glucose monitor and quantified as total AUC (tAUC). Compared to SIT, plasma glucose iAUC was reduced by 33% [3.4 ± 1.0 vs 5.1 ± 1.0 (mean ± SEM) mmol h·L-1, p = 0.019] and plasma insulin iAUC by 41% (813 ± 224 vs 1373 ± 224, p = 0.033 pmol h·L-1) for the ACB condition. During the ACB condition there was a significant reduction in interstitial glucose tAUC (24.4 ± 5.2 vs 26.9 ± 5.2 mmol h·L-1, p < 0.001), but this did not persist beyond the laboratory observation period. CONCLUSIONS: Regular brief light-intensity activity bouts can attenuate glycemic responses during television viewing time following a high-energy evening meal in overweight/obese adults.

Breaking up prolonged sitting reduces resting blood pressure in overweight/obese adults.

AIM: To compare the effect of 7 h of prolonged sitting on resting blood pressure with a similar duration of sitting combined with intermittent brief bouts of light-intensity or moderate-intensity physical activity. METHODS AND RESULTS: Overweight/obese adults (n = 19; aged 45-65 years) were recruited for a randomized three-treatment crossover trial with a one-week washout between treatments: 1) uninterrupted sitting; 2) sitting with 2 min bouts of light-intensity walking at 3.2 km/h every 20 min; and, 3) sitting with 2 min bouts of moderate-intensity walking at between 5.8 and 6.4 km/h every 20 min. After an initial 2 h period seated, participants consumed a test meal (75 g carbohydrate, 50 g fat) and completed each condition over the next 5 h. Resting blood pressure was assessed oscillometrically every hour as a single measurement, 5 min prior to each activity bout. GEE models were adjusted for sex, age, BMI, fasting blood pressure and treatment order. After adjustment for potential confounding variables, breaking up prolonged sitting with light and moderate-intensity activity breaks was associated with lower systolic blood pressure [light: 120 ± 1 mmHg (estimated marginal mean ± SEM), P = 0.002; moderate: 121 ± 1 mmHg, P = 0.02], compared to uninterrupted sitting (123 ± 1 mmHg). Diastolic blood pressure was also significantly lower during both of the activity conditions (light: 76 ± 1 mmHg, P = 0.006; moderate: 77 ± 1 mmHg, P = 0.03) compared to uninterrupted sitting (79 ± 1 mmHg). No significant between-condition differences were observed in mean arterial pressure or heart rate. CONCLUSION: Regularly breaking up prolonged sitting may reduce systolic and diastolic blood pressure. TRIAL REGISTRATION NUMBER: ACTRN12609000656235 (http://www.anzctr.org.au) TRIAL REGISTRATION DATE: August 4th 2009.

Ephedrine activates brown adipose tissue in lean but not obese humans.

AIMS/HYPOTHESIS: Brown adipose tissue (BAT) activation increases energy consumption and may help in the treatment of obesity. Cold exposure is the main physiological stimulus for BAT thermogenesis and the sympathetic nervous system, which innervates BAT, is essential in this process. However, cold-induced BAT activation is impaired in obese humans. To explore the therapeutic potential of BAT, it is essential to determine whether pharmacological agents can activate BAT. METHODS: We aimed to determine whether BAT can be activated in lean and obese humans after acute administration of an orally bioavailable sympathomimetic. In a randomised, double-blinded, crossover trial, we administered 2.5 mg/kg of oral ephedrine to nine lean (BMI 22 ± 1 kg/m²) and nine obese (BMI 36 ± 1 kg/m²) young men. On a separate day, a placebo was administered to the same participants. BAT activity was assessed by measuring glucose uptake with [¹8F]fluorodeoxyglucose and positron emission tomography-computed tomography imaging. RESULTS: BAT activity was increased by ephedrine compared with placebo in the lean, but unchanged in the obese, participants. The change in BAT activity after ephedrine compared with placebo was negatively correlated with various indices of body fatness. CONCLUSIONS/INTERPRETATION: BAT can be activated via acute, oral administration of the sympathomimetic ephedrine in lean, but not in obese humans.

Large artery biomechanics and diastolic dysfunctionin patients with Type 2 diabetes.

AIMS: To comprehensively characterize large artery biomechanical properties and examine their relationship to cardiac function in patients with Type 2 diabetes mellitus (DM). METHODS: Fifty-five individuals with Type 2 DM were compared with 66 age- and sex-matched healthy control subjects. Arterial biomechanical properties were assessed by systemic arterial compliance (SAC; two-element Windkessel model), carotid-femoral pulse wave velocity (PWVc-f), femoral-dorsalis pedis pulse wave velocity (PWVf-d) and carotid augmentation index. Cardiac structure and function were assessed by echocardiography. RESULTS: Individuals with Type 2 DM had lower SAC and higher PWVc-f when compared with the healthy population. The PWVc-f was significantly lower than the PWVf-d in control individuals, but this difference was not evident in individuals with Type 2 DM due to higher PWVc-f. Augmentation index was similar in both groups, but the time to the first systolic inflection (time to reflection) was shorter in the individuals with Type 2 DM. The individuals with Type 2 DM had a greater prevalence of diastolic abnormalities when compared with the control group. Arterial stiffness indices, including SAC and pulse pressure, correlated with left ventricular filling pressure (defined as peak velocity during early diastolic filling divided by the velocity of movement of the mitral valve annulus in early diastole; r = -0.33 and 0.36 respectively. CONCLUSIONS: Patients with Type 2 DM on standard medication showed preferential stiffening of the large central arteries. However, carotid augmentation index was not different between the two groups and is therefore not a reliable indicator of large artery stiffening in this patient group. Diastolic dysfunction, present in a significant proportion of this population with Type 2 DM, was closely associated with arterial stiffening, suggesting a common aetiology.

Novel pharmacological approaches to combat obesity and insulin resistance: targeting skeletal muscle with 'exercise mimetics'.

Chronic diseases arising from obesity will continue to escalate over coming decades. Current approaches to combating obesity include lifestyle measures, surgical interventions and drugs that target weight reduction or the metabolic consequences of obesity. Lifestyle measures including physical activity are usually the primary strategy, but these are of limited long-term efficacy because of failure to maintain behavioural change. An alternative approach used to elicit the benefits of exercise training and overcome the problems of long-term compliance is to develop drugs that mimic aspects of the trained state. Elucidation of metabolic pathways responsive to exercise in various tissues, particularly skeletal muscle, was an important antecedent to the promising concept of drugs that may mimic specific aspects of the exercise response. From an obesity perspective, an important aim is to develop an agent that reduces body fat and improves metabolic homeostasis. This review focuses on promising metabolic signalling pathways in skeletal muscle that may yield 'exercise mimetic' targets.

Human brown adipose tissue as a target for obesity management; beyond cold-induced thermogenesis.

Elevating energy expenditure via adaptive thermogenesis in brown adipose tissue (BAT) is a potential strategy to reverse obesity. Much early enthusiasm for this approach, based on rodent studies, was tempered by the belief that BAT was relatively inconsequential in healthy adult humans. Interest was reinvigorated a decade ago when a series of studies re-identified BAT, primarily in upper thoracic regions, in adults. Despite the ensuing explosion of pre-clinical investigations and identification of an extensive list of potential target molecules for BAT recruitment, our understanding of human BAT physiology remains limited, particularly regarding interventions which might hold therapeutic promise. Cold-induced BAT thermogenesis (CIT) has been well studied, although is not readily translatable as an anti-obesity approach, whereas little is known regarding the role of BAT in human diet-induced thermogenesis (DIT). Furthermore, human studies dedicated to translating known pharmacological mechanisms of adipose browning from animal models are sparse. Several lines of recent evidence suggest that molecular regulation and physiology of human BAT differ to that of laboratory rodents, which form the majority of our knowledge base. This review will summarize knowledge on CIT and expand upon the current understanding and evidence gaps related to human adaptive thermogenesis via mechanisms other than cold.

Diurnal variation in endothelium-dependent vasodilatation is not apparent in coronary artery disease.

BACKGROUND: Acute coronary syndromes present with an increased incidence from 6:00 AM to 12:00 noon. Whether endothelial function follows a diurnal rhythm and whether this rhythm is impaired in coronary artery disease (CAD) has not previously been studied. METHODS AND RESULTS: Diurnal variation in endothelium-dependent vasodilatation was examined in 10 CAD patients and 10 control subjects. Forearm blood flow responses to acetylcholine, sodium nitroprusside, and N(G)-monomethyl-L-arginine were determined by plethysmography at 8:00 AM, 2:00 PM, and 8:00 PM. Heart rate, blood pressure, plasma cortisol, and inflammatory markers were also determined. Heart rate and the low-frequency component of heart rate variability were greatest in the morning in control subjects, suggesting a diurnal variation in sympathetic activity. Basal forearm blood flows were significantly reduced in control subjects at 8:00 PM compared with 8:00 AM and 2:00 PM (1.2+/-0.2 versus 2.1+/-0.2 [8:00 AM] and 2.1+/-0.3 [2:00 PM] mL. 100 mL(-1). min(-1); P<0.05) but unchanged in the CAD group. Acetylcholine (37 microgram/min) responses were greater at 8:00 AM than at 8:00 PM in control subjects (12.5+/-3.7 versus 19.6+/-2.9 mL. 100 mL(-1). min(-1), respectively; P<0.05), but these responses were not time dependent in the CAD group. Responses to sodium nitroprusside were similar at all time points and between those with and without CAD. CONCLUSIONS: Thus, normal volunteers have a diurnal variation in their endothelium-dependent vasodilatation that may counteract other, potentially adverse, diurnal variations in hemodynamic and other parameters. In contrast, CAD patients who had presented with acute coronary syndromes showed a loss of this protective mechanism.

Nitric oxide synthase inhibition reduces leg glucose uptake but not blood flow during dynamic exercise in humans.

Nitric oxide (NO) appears to play a role in contraction-stimulated glucose uptake in isolated rodent skeletal muscle; however, no studies have examined this question in humans. Seven healthy men completed two 30-min bouts of supine cycling exercise at 60 +/- 2% peak pulmonary oxygen uptake (VO2 peak), separated by 90 min of rest. The NO synthase inhibitor N(G)-monomethyl-L-arginine ([L-NMMA]; total dose 5 mg/kg body weight) or saline (control) were administered via the femoral artery for the final 20 min of exercise in a randomized blinded crossover design. L-Arginine (5 mg/kg body weight) was co-infused during the final 5 min of each exercise bout. Leg blood flow (LBF) was measured by thermodilution in the femoral vein, and leg glucose uptake was calculated as the product of LBF and femoral arteriovenous (AV) glucose difference. L-NMMA infusion significantly (P < 0.05) reduced leg glucose uptake compared with control (48 +/- 12% lower at 15 min, mean +/- SE). The reduction in glucose uptake was due solely to a decrease in AV glucose difference, as there was no effect of L-NMMA infusion on LBF during exercise. Co-infusion of L-arginine restored glucose uptake during L-NMMA infusion to levels similar to control. These results indicate that NO production contributes substantially to exercise-mediated skeletal muscle glucose uptake in humans independent of skeletal muscle blood flow.

Pulse pressure--a review of mechanisms and clinical relevance.

The goal of this study was to review the origin, clinical relevance and treatment of pulse pressure (PP). Elevated PP is increasingly being recognized as a risk factor for cardiovascular, particularly coronary, disease. Pulse pressure is discussed in terms of both Windkessel and distributive models of the arterial circulation. Pulse pressure arises from the interaction of cardiac ejection (stroke volume) and the properties of the arterial circulation. An increased stiffness of the aorta and large arteries leads to an increase in PP through a reduction in arterial compliance and effects on wave reflection. A number of factors are known to influence arterial wall behavior and, therefore, PP. In addition to the effects of aging and blood pressure on arterial wall elasticity, there is some evidence that atherosclerosis, per se, amplifies these effects. Thus, the relationship between PP and coronary disease may be bidirectional. A number of dietary and lifestyle interventions have been shown to modify large artery behavior. These include aerobic exercise training and consumption of n-3 fatty acids. Conversely, strength training is associated with an increase in arterial stiffness and a higher PP. The effects of antihypertensive medication have been extensively studied, but many studies are difficult to interpret because of concomitant change in blood pressure, and to a lesser degree, heart rate. However a number of studies do suggest direct arterial wall effects, particularly for angiotensin-converting enzyme inhibitors. A distributed compliance model of the arterial circulation provides a framework for understanding the causes, effects and potential treatment of elevations in PP.

Hormonal therapy increases arterial compliance in postmenopausal women.

OBJECTIVES: This study investigated the effects of hormonal therapy on large arterial properties. BACKGROUND: Arterial stiffness is an emerging risk marker for coronary heart disease and is potentially modifiable. Postmenopausal use of hormonal therapy is associated with a lower risk of coronary heart disease. METHODS: Total systemic arterial compliance (SAC) and pulse wave velocity (PWV) were determined in 26 premenopausal and 52 postmenopausal women, 26 of whom were taking hormonal therapy. RESULTS: Arterial compliance was greater in the premenopausal group (mean +/- SEM 0.57 +/- 0.04 arbitrary compliance units [ACU]) than in the postmenopausal group not taking hormonal therapy (0.26 +/- 0.02 ACU, p = 0.001). Postmenopausal women taking hormonal therapy had a significantly increased total SAC compared with women not taking hormonal therapy (0.43 +/- 0.02 vs. 0.26 +/- 0.02 ACU, p = 0.001). PWV in the aortofemoral region in the premenopausal women was 6.0 +/- 0.2 vs. 8.9 +/- 0.3 m/s (p < 0.001) in untreated postmenopausal women. However, postmenopausal women taking hormonal therapy had a significantly lower PWV than those not taking hormonal therapy (7.9 +/- 0.2 vs. 8.9 +/- 0.3 m/s, p = 0.01). Eleven postmenopausal women had their hormone replacement therapy withdrawn for 4 weeks, resulting in a significant decrease in SAC and a significant increase in aortofemoral PWV. CONCLUSIONS: The increased SAC and decreased PWV in women receiving hormonal therapy suggest that such therapy may decrease stiffness of the aorta and large arteries in postmenopausal women, with potential benefit for age-related cardiovascular disorders. The reduction of arterial compliance with age appears to be altered with hormonal therapy.

Spontaneous running increases aortic compliance in Wistar-Kyoto rats.

OBJECTIVE: Previous studies in humans have found, using non-invasive methodology, that arterial compliance is elevated with exercise training. Forced exercise in animals has corroborated these findings, but the association of this type of exercise with psychological stressors limits its relevance to humans. We have investigated the effects of spontaneous running exercise from 4-20 weeks of age on aortic and mesenteric compliance and vascular reactivity in Wistar-Kyoto (WKY) rats. METHODS: Animals were killed using CO2 asphyxia and the aorta, mesentery and heart rapidly removed. The heart was dissected and weighed. The aorta was separated into 3 4-mm rings which were mounted on wires in organ baths for determination of compliance and vascular reactivity to noradrenaline, acetylcholine and sodium nitroprusside. The slope of diameter-pressure relationship derived using Laplace's equation was used as an index of compliance. RESULTS: During the final 2 weeks of training WKY rats ran an average of 7.9 +/- 1.0 km/24 h. Body weight was not affected by training. Training significantly increased the weight of the atria, left and right ventricles as well as total heart weight and left ventricular/body weight ratio. Aortic compliance was increased from 12.3 +/- 0.4 to 14.2 +/- 0.5 microns/mmHg (P < 0.05) after training. There was no effect of training on aortic reactivity to noradrenaline, acetylcholine or sodium nitroprusside. CONCLUSION: Exercise training increased intrinsic aortic compliance in WKY rats which provides evidence for a structural basis for the elevated compliance reported previously with 4 weeks of aerobic exercise in man.

Genetic manipulation of cardiac Hsp72 levels does not alter substrate metabolism but reveals insights into high-fat feeding-induced cardiac insulin resistance.

Heat shock protein 72 (Hsp72) protects cells against a variety of stressors, and multiple studies have suggested that Hsp72 plays a cardioprotective role. As skeletal muscle Hsp72 overexpression can protect against high-fat diet (HFD)-induced insulin resistance, alterations in substrate metabolism may be a mechanism by which Hsp72 is cardioprotective. We investigated the impact of transgenically overexpressing (Hsp72 Tg) or deleting Hsp72 (Hsp72 KO) on various aspects of cardiac metabolism. Mice were fed a normal chow (NC) or HFD for 12 weeks from 8 weeks of age to examine the impact of diet-induced obesity on metabolic parameters in the heart. The HFD resulted in an increase in cardiac fatty acid oxidation and a decrease in cardiac glucose oxidation and insulin-stimulated cardiac glucose clearance; however, there was no difference in Hsp72 Tg or Hsp72 KO mice in these rates compared with their respective wild-type control mice. Although HFD-induced cardiac insulin resistance was not rescued in the Hsp72 Tg mice, it was preserved in the skeletal muscle, suggesting tissue-specific effects of Hsp72 overexpression on substrate metabolism. Comparison of two different strains of mice (BALB/c vs. C57BL/6J) also identified strain-specific differences in regard to HFD-induced cardiac lipid accumulation and insulin resistance. These strain differences suggest that cardiac lipid accumulation can be dissociated from cardiac insulin resistance. Our study finds that genetic manipulation of Hsp72 does not lead to alterations in metabolic processes in cardiac tissue under resting conditions, but identifies mouse strain-specific differences in cardiac lipid accumulation and insulin-stimulated glucose clearance.

Relation between coronary artery disease, aortic stiffness, and left ventricular structure in a population sample.

To elucidate the relationship between coronary artery disease (CAD), aortic stiffness, and left ventricular structure, we recruited 55 subjects (33 men; average age, 63+/-1 years) with previously unknown CAD from a healthy general population sample, as well as 55 control subjects matched for gender, age, and serum cholesterol level. We measured arterial blood pressure and the systolic expansion of the transverse aorta and left ventricular structure by echocardiography. Aortic stiffness was higher in CAD patients than in controls, with a brachial pulse pressure of 59+/-3 versus 52+/-2 mm Hg and stiffness indices of Ep=212+/-26 versus 123+/-13 kN/m2 and beat=16+/-2 versus 9+/-1 (all P<0.01). Mean arterial pressure was similar in both groups during the measurements (95+/-2 versus 93+/-2 mm Hg, P=NS). Most CAD patients (61%) were in the highest stiffness quartile defined by the normal control values (P<0.05 versus control). Left ventricular mass index was also higher in CAD patients than in matched controls (139+/-5 versus 123+/-4 g/m2, P<0.05). We conclude that aortic stiffness and left ventricular mass are increased in subjects newly diagnosed as having CAD. This might explain previously reported associations of an increased mortality, particularly from CAD, found among subjects with elevated pulse pressures.

Muscular strength training is associated with low arterial compliance and high pulse pressure.

Aerobic exercise training increases arterial compliance and reduces systolic blood pressure, but the effects of muscular strength training on arterial mechanical properties are unknown. We compared blood pressure, whole body arterial compliance, aortic impedance, aortic stiffness (measured by beta-index and carotid pulse pressure divided by normalized systolic expansion [Ep]), pulse wave velocity, and left ventricular parameters in 19 muscular strength-trained athletes (mean+/-SD age, 26+/-4 years) and 19 sedentary controls (26+/-5 years). Subjects were healthy, non-steroid-using, nonsmoking males, and athletes had been engaged in a strength-training program with no aerobic component for a minimum of 12 months. There was no difference in maximum oxygen consumption between groups, but handgrip strength (mean+/-SEM, 44+/-2 versus 56+/-2 kg; P<0.01) and left ventricular mass (168+/-8 versus 190+/-8 g; P<0.05) were greater in athletes. Arterial stiffness was higher in athletes, as evidenced by lower whole body arterial compliance (0.40+/-0.04 versus 0.54+/-0.04 arbitrary compliance units; P=0.01), higher aortic characteristic impedance (1.55+/-0.13 versus 1.18+/-0.08 mm Hg. s. cm-1; P<0.05), beta-index (4.6+/-0.2 versus 3.8+/-0.4; P<0. 05), and ln Ep (10.86+/-0.06 versus 10.60+/-0.08; P<0.01). Femoral-dorsalis pedis pulse wave velocity was also higher in the athletes, but carotid-femoral pulse wave velocity was not different. Furthermore, both carotid (56+/-3 versus 44+/-2 mm Hg; P<0.001) and brachial (60+/-3 versus 50+/-2 mm Hg; P<0.01) pulse pressures were higher in the athletes, but mean arterial pressure and resting heart rate did not differ between groups. These data indicate that both the proximal aorta and the leg arteries are stiffer in strength-trained individuals and contribute to a higher cardiac afterload.

Variations in endothelial function and arterial compliance during the menstrual cycle.

Female sex hormones have been implicated in the cardioprotection of premenopausal women. However, the cardiovascular actions of these hormones and the effects of their natural fluctuations during the menstrual cycle are not fully understood. We studied changes in vascular function during the menstrual cycle in 15 healthy premenopausal women. Four noninvasive procedures were performed during the early follicular (EF), late follicular (LF), early luteal (EL), and late luteal (LL) phases: flow-mediated dilatation (FMD) of the brachial artery during reactive hyperemia, laser Doppler velocimetry (LDV) with direct current iontophoresis of acetylcholine (ACh) and nitroprusside, whole body arterial compliance (WBAC), and pulse wave velocity. Hormone levels were consistent with predicted cycle phase and showed that all subjects ovulated during the cycle studied. FMD, LDV with ACh, and WBAC varied cyclically, with significant increases from the F to LF phase, sharp falls in the EL phase, and significant recoveries in the LL phase. These changes were most marked for FMD [EF, 8.8 +/- 0.6% (mean +/- SEM); LF, 10.0 +/- 0.7; EL, 4.2 +/- 0.6; LL, 8.6 +/- 0.9] and the LDV response to ACh (EF, 2.7 +/- 0.2 V/min; LF, 3.3 +/- 0.4; EL, 1.8 +/- 0.3; LL, 2.7 +/- 0.4). WBAC changed similarly (EF, 0.58 +/- 0.08 arbitrary units; LF, 0.84 +/- 0.06; EL, 0.65 +/- 0.05; LL, 0.68 +/- 0.06). Sodium nitroprusside-induced vasodilatation decreased significantly from EF to EL, with no other significant difference, and pulse wave velocity did not vary significantly over the four time points. Conductance and resistance artery endothelial reactivity and smooth muscle sensitivity to nitric oxide and arterial compliance are modulated significantly in response to the changing hormonal patterns of the menstrual cycle. These findings emphasize the importance of menstrual phase in the interpretation of data on endothelial function and may provide insights into the mechanisms underlying sex differences in cardiovascular risk and other disease processes in premenopausal women.

The effects of voluntary running on cardiac mass and aortic compliance in Wistar-Kyoto and spontaneously hypertensive rats.

OBJECTIVE: To investigate the effects of voluntary running exercise from 4-20 weeks of age on aortic compliance in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). DESIGN: For each species we made comparisons between rats housed with an exercise wheel locked (10 rats) and unlocked (10 rats). METHODS: Rats were killed using CO2 asphyxia and the aorta and heart of each rat were rapidly removed. The heart was dissected and weighed. A 4 mm descending proximal aortic ring was mounted on wires in an organ bath for determination of static compliance from the slope of the diameter-pressure relationship derived using Laplace's equation. RESULTS: During the final 2 weeks of training WKY rats ran an average of 7.9 +/- 1.0 km/24 h compared with 1.0 +/- 0.2 km/24 h for SHR. Body weights of WKY rats and SHR and of animals housed with locked and unlocked exercise wheels did not differ. The septum, left ventricle and total heart weights and left ventricular:body weight ratios of sedentary SHR were greater than those of sedentary WKY rats. Trained WKY rats had significantly higher atrial, left and right ventricular and total heart weights and left ventricular:body weight ratios than did untrained WKY rats. Aortic compliance was higher in trained than it was in sedentary WKY rats (12.3 +/- 0.4 versus 14.2 +/- 0.5 microm/mmHg, P < 0.05). There was no difference between heart weights and aortic compliances of SHR housed with exercise wheels locked and unlocked. CONCLUSION: Exercise-trained WKY rats had greater intrinsic aortic compliance when it was measured statically in vitro, which supports results of previous human work revealing a blood-pressure-independent component in the elevation of arterial compliance with training. The lower physical activity of the SHR strain used in this study could contribute to their higher blood pressures and lack of change in aortic compliance with exercise training.

Women exhibit a greater age-related increase in proximal aortic stiffness than men.

BACKGROUND: Large artery mechanical properties are a major determinant of pulse pressure and cardiovascular outcome. Sex differences in these properties may underlie the variation in cardiovascular risk profile between men and women, in relation to age. OBJECTIVE: To investigate sex differences in the age-related stiffening of large arteries. DESIGN: Cross-sectional. METHODS: One hundred and twenty healthy men and women were recruited and divided equally into tertiles by age: young (mean +/- SD, 23 +/- 5 years), middle-age (47 +/- 3 years) and older (62 +/- 7 years). Lipids, mean arterial pressure and heart rate were matched within each tertile. Carotid tonometry and Doppler velocimetry were used to measure indices of large artery stiffness. RESULTS: There was no sex difference in systemic arterial compliance (SAC) in the young group (mean +/- SEM, 0.61 +/- 0.05 arbitrary compliance units (ACU) in women compared with 0.67 +/- 0.04 ACU in men), but in the older population women had lower SAC than men (0.27 +/- 0.03 ACU compared with 0.57 +/- 0.04 ACU respectively; P < 0.001). Measures independent of aortic geometry (distensibility index and aortic impedance) indicated that stiffness was lower in young women than in men (P < 0.05), but the reverse was true in the older population (P < 0.01). This paralleled the brachial and carotid pulse pressures, which were lower in young (P < 0.01) and higher in older women compared with those in men (P < 0.05). Follicle stimulating hormone concentrations correlated strongly (r values 0.39-0.65) with all indices of central, but not peripheral, arterial function, whereas concentrations of luteinizing hormone, progesterone and oestradiol correlated less strongly. CONCLUSIONS: In men and women matched for mean pressures, the age-related stiffening of large arteries is more pronounced in women, which is consistent with changes in female hormonal status.

Withdrawal of hormonal therapy for 4 weeks decreases arterial compliance in postmenopausal women.

BACKGROUND: We demonstrated in a previous cross-sectional study that arterial compliance is elevated in postmenopausal women taking estrogen-containing hormonal therapy, which may partially account for the reduction in cardiovascular risk observed. OBJECTIVE: To investigate the effects of withdrawal and recommencement of hormonal therapy, each for 4 weeks, on arterial compliance. METHODS: Seventeen postmenopausal women [aged 56 +/- 4 years (mean +/- SD)] taking long-term hormonal therapy (+HT group) were studied at baseline, 4 weeks after withdrawal of hormonal therapy and again 4 weeks after recommencement. Systemic arterial compliance (SAC), pulse wave velocity (PWV) in the aorto-femoral and femoral-dorsalis pedis regions, and hemodynamic variables were measured at baseline, and at the end of each study intervention. As a time-control, seventeen postmenopausal women (aged 63 +/- 7 years) not taking hormonal therapy (-HT group) were also investigated. RESULTS: SAC significantly decreased from 0.47 +/- 0.06 to 0.40 +/- 0.05 arbitrary compliance units (mean +/- SEM; P < 0.05) after 4 weeks withdrawal from hormonal therapy. PWV in the femoral-dorsalis pedis region was elevated significantly by the withdrawal of hormonal therapy (8.4 +/- 0.4 to 9.4 +/- 0.5 m/s; P < 0.05), but PWV in the aortofemoral region did not change. After therapy had been recommenced for 4 weeks, SAC and PWV in the femoral-dorsalis pedis region were restored to baseline values. The -HT group showed no difference in SAC or PWV, and mean arterial pressure did not change in either group throughout the study period. CONCLUSION: These data suggest that hormonal modulation of distal arterial vascular tone may account for short-term changes in arterial compliance associated with estrogen-containing hormonal therapy.

Gender differences in the timing of arterial wave reflection beyond differences in body height.

OBJECTIVES: The timing of arterial wave reflection affects the shape of the arterial waveform and thus is a major determinant of pulse pressure. This study assessed differences in wave reflection between genders beyond the effect of body height. METHODS: From 1123 elderly (aged 71 +/- 5 years) currently untreated hypertensives, we selected 104 pairs of men and women with identical body height (average 164 +/- 4 cm). All subjects underwent echocardiography, including measurement of aortic arch expansion, automated blood pressure measurements, measurement of ascending aortic blood flow and simultaneous carotid artery tonometry. RESULTS: Women had higher pulse (80 +/- 17 versus 74 +/- 17 mmHg, P < 0.05) and lower diastolic pressure (79 +/- 11 versus 82 +/- 10 mmHg, P < 0.05). Whilst heart rate was similar, women had a longer time to the systolic peak (210 +/- 28 versus 199 +/- 34 ms, P < 0.01) and a longer ejection time (304 +/- 21 versus 299 +/- 25 ms, P < 0.001). Wave reflection occurred earlier in women (time between maxima 116 +/- 55 versus 132 +/- 47 ms, P < 0.05) and augmentation index was higher (36 +/- 11 versus 28 +/- 12%, P < 0.001). Aortic diameter was smaller in women and the aortic arch was stiffer (median Ep 386 versus 302 kN/m2, P < 0.05). Hence, systemic arterial compliance was less in women (0.8 +/- 0.2 versus 1.0 +/- 0.3 ml/mmHg). CONCLUSIONS: We conclude that elderly hypertensive men and women have a different timing of both left ventricular ejection and arterial wave reflection when both genders are matched for body height. Women have smaller and stiffer blood vessels resulting in an earlier return of the reflected wave, which is likely due to an increased pulse wave velocity in women.

Higher systemic arterial compliance is associated with greater exercise time and lower blood pressure in a young older population.

OBJECTIVES: Arterial compliance is an important therapeutic target in older individuals in whom stiffening of the proximal arterial circulation is thought to underlie systolic hypertension and increased cardiac work. We have shown previously that arterial compliance is related to aerobic fitness and that it is increased in young (20 to 35 years old), previously sedentary individuals by a 4-week period of moderate aerobic training. The extent to which compliance relates to exercise performance in a random selection of young older patients has not been reported previously. Therefore, we examined the interrelationship between systemic arterial compliance (SAC) and time to cessation of exercise during a standard treadmill exercise test in an older population. DESIGN: A cross-sectional survey. METHODS: SAC was estimated at rest using simultaneous recordings of ascending aortic flow and carotid applanation tonometry in 43 subjects aged 67 +/- 7 years (mean +/- SD; 24 men and 19 women). Treadmill exercise testing was performed using a modified Bruce protocol. Aerobic capacity was assessed as Heart Rate-Blood Pressure product and exercise tolerance as total treadmill time. RESULTS: SAC and exercise tolerance were related to gender, with men exhibiting greater exercise reserve and higher SAC than women. There was a significant positive correlation between SAC and time to cessation of exercise (r = .34; P = .03), with a negative correlation between SAC and resting heart rate-blood pressure product (r = -.66; P < .001). SAC was correlated with height and blood pressure. Exercise tolerance was related to height (P < .02). CONCLUSIONS: These data indicate a positive association between SAC and fitness level in healthy older people and an inverse association between SAC and systolic blood pressure. Our findings are consistent with either (1) acquisition of a more compliant circulation and lower blood pressure through more physical activity or (2) that a more compliant arterial circulation and lower blood pressure permit greater athletic performance.