Baroreflex buffering is reduced with age in healthy men

Background— Baroreflex buffering is an important mechanism in arterial blood pressure control. The effect of healthy (physiological) aging on tonic baroreflex buffering in humans is unknown. Methods and Results— Baroreflex buffering was determined in 27 young (aged 25±1 years) and 16 older (aged 65±1 years) healthy normotensive men by measuring the potentiation of the systolic blood pressure (SBP) responses to a phenylephrine bolus (BRBbolus) and incremental infusion (BRBslope) during compared with before ganglionic blockade with trimethaphan. The SBP responses to phenylephrine either were not different or greater in the older men before ganglionic blockade, but smaller during ganglionic blockade. BRBbolus (2.1±0.4 versus 5.1±0.7, P<0.001) and BRBslope (1.6±0.2 versus 3.5±0.4, P<0.0001) were ≈115% smaller in the older men. Baroreflex buffering was not consistently related to mean levels or variability of blood pressure or heart rate, or to cardiovagal baroreflex sensitivity, but correlated with muscle sympathetic nerve activity (BRBbolus: r=−0.55, BRBslope: r=−0.69, P<0.005) and the SBP responses to phenylephrine during ganglionic blockade (BRBbolus: r=0.53; BRBslope: r=0.98, P<0.0001). BRBbolus was also inversely related to the SBP response to phenylephrine before ganglionic blockade (r=−0.78, P<0.0001). Conclusions— Physiological aging in men is associated with a marked reduction in baroreflex buffering. The decrease in baroreflex buffering with aging is related to increases in basal sympathetic nerve activity and reductions in systemic α1–adrenergic vascular responsiveness. These findings are helpful for interpreting changes in baroreflex buffering in older patients with cardiovascular disease, as well as changes in responsiveness to vasoactive drugs with aging

Comparative Approaches to Understanding the Relation between Aging and Physical Function

Despite dedicated efforts to identify interventions to delay aging, most promising interventions yielding dramatic life-span extension in animal models of aging are often ineffective when translated to clinical trials. This may be due to differences in primary outcomes between species and difficulties in determining the optimal clinical trial paradigms for translation. Measures of physical function, including brief standardized testing batteries, are currently being proposed as biomarkers of aging in humans, are predictive of adverse health events, disability, and mortality, and are commonly used as functional outcomes for clinical trials. Motor outcomes are now being incorporated into preclinical testing, a positive step toward enhancing our ability to translate aging interventions to clinical trials. To further these efforts, we begin a discussion of physical function and disability assessment across species, with special emphasis on mice, rats, monkeys, and man. By understanding how physical function is assessed in humans, we can tailor measurements in animals to better model those outcomes to establish effective, standardized translational functional assessments with aging

Women have lower tonic autonomic support of arterial blood pressure and less effective baroreflex buffering than men

BACKGROUND: Short-term and tonic regulation of arterial blood pressure (BP) differ in premenopausal women and men of similar age. The autonomic nervous system (ANS) plays a critical role in BP regulation. METHODS AND RESULTS: To test the hypothesis that women have lower tonic ANS support of BP (reduction in intra-arterial BP during acute ganglionic blockade [GB] with intravenous trimethaphan) and less effective baroreflex buffering (BRB) of BP (potentiation of the systolic BP [SBP] response to bolus phenylephrine during versus before GB) than men, 51 healthy adults, 22 premenopausal women (aged 28+/-1 years, mean+/-SE) and 29 men (aged 27+/-1 years), were studied. Women had lower baseline SBP and plasma catecholamine concentrations than men (P<0.05). Tonic ANS support of BP was approximately 50% to 65% lower in the women (P<0.001). The reductions in BP during GB were related to baseline plasma catecholamine concentrations (r=-0.31 to -0.41, P<0.05). Acute BRB of BP was 47% smaller in the women (3.3+/-0.5 versus 6.3+/-0.9, P=0.006) and was related to the SBP responses to phenylephrine before GB (R2=0.71, P<0.0001). Systemic alpha1-adrenergic vascular responsiveness (SBP response to bolus phenylephrine during GB) was not different (women 21.5+/-2 mm Hg versus men 18.6+/-2 mm Hg, P=0.3). CONCLUSIONS: Premenopausal women have lower tonic sympathoadrenal activity-related ANS support of BP and less effective BRB of BP than men of similar age. The lower tonic ANS support of BP could contribute to the lower chronic BP levels of premenopausal women, whereas attenuated BRB of BP may help explain less effective BP regulation in women in response to vasoactive drugs and acute stress

Dietary Nitrate and Nitric Oxide Metabolism: Mouth, Circulation, Skeletal Muscle, and Exercise Performance

Nitric oxide (NO) is a gaseous signaling molecule that plays an important role in myriad physiological processes, including the regulation of vascular tone, neurotransmission, mitochondrial respiration, and skeletal muscle contractile function. NO may be produced via the canonical NO synthase-catalyzed oxidation of l-arginine and also by the sequential reduction of nitrate to nitrite and then NO. The body's nitrate stores can be augmented by the ingestion of nitrate-rich foods (primarily green leafy vegetables). NO bioavailability is greatly enhanced by the activity of bacteria residing in the mouth, which reduce nitrate to nitrite, thereby increasing the concentration of circulating nitrite, which can be reduced further to NO in regions of low oxygen availability. Recent investigations have focused on promoting this nitrate-nitrite-NO pathway to positively affect indices of cardiovascular health and exercise tolerance. It has been reported that dietary nitrate supplementation with beetroot juice lowers blood pressure in hypertensive patients, and sodium nitrite supplementation improves vascular endothelial function and reduces the stiffening of large elastic arteries in older humans. Nitrate supplementation has also been shown to enhance skeletal muscle function and to improve exercise performance in some circumstances. Recently, it has been established that nitrate concentration in skeletal muscle is much higher than that in blood and that muscle nitrate stores are exquisitely sensitive to dietary nitrate supplementation and deprivation. In this review, we consider the possibility that nitrate represents an essential storage form of NO and discuss the integrated function of the oral microbiome, circulation, and skeletal muscle in nitrate-nitrite-NO metabolism, as well as the practical relevance for health and performance

Associations Between Age and Resting State Connectivity Are Partially Dependent Upon Cardiovascular Fitness

Previous research suggests a marked impact of aging on structural and functional connectivity within the frontoparietal control network (FPCN) and default mode network (DMN). As aging is also associated with reductions in cardiovascular fitness, age-related network connectivity differences reported by past studies could be partially due to age-related declines in fitness. Here, we use data collected as part of a 16-week exercise intervention to explore relationships between fitness and functional connectivity. Young and older adults completed baseline assessments including cardiovascular fitness, health and functioning measures, and an fMRI session. Scan data were acquired on a Siemens 3T MRI scanner with a 32-channel head coil. Results from regression analyses indicated that average connectivity did not differ between young and older adults. However, individual ROI-to-ROI connectivity analyses indicated weaker functional correlations for older adults between specific regions in the FPCN and DMN and, critically, many of these differences were attenuated when fitness was accounted for. Taken together, findings suggest that fitness exerts regional rather than global effects on network connectivity. Copyright © 2022 Gust, Moe, Seals, Banich, Andrews-Hanna, Hutchison and Bryan.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Transgenic mice expressing human IL-32 develop adipokine profiles resembling those of obesity-induced metabolic changes

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Increased thermogenic responsiveness to intravenous beta-adrenergic stimulation in habitually exercising humans is not related to skeletal muscle beta2-adrenergic receptor density

Habitually exercising adults demonstrate greater thermogenic responsiveness to beta-adrenergic receptor (beta-AR) stimulation compared with their sedentary peers, but the molecular mechanisms involved are unknown. To determine the possible role of increased beta-AR density, we studied 32 healthy adults: 17 habitual aerobic exercisers (age 45 +/- 5 years, 11 males) and 15 sedentary (49 +/- 5 years, 7 males). Maximal oxygen uptake (43.7 +/- 2.5 versus 31.6 +/- 2.9 ml kg(-1) min(-1), P = 0.002, mean +/- S.E.M.) and vastus lateralis muscle maximal citrate synthase activity (1.70 +/- 0.36 versus 0.58 +/- 0.11 micromol min(-1) g(-1), P = 0.008) were higher in the habitually exercising subjects. Resting energy expenditure (EE) adjusted for fat-free mass (FFM) was similar in the habitually exercising (5903 +/- 280 kJ day(-1)) and sedentary adults (6054 +/- 289 kJ day(-1), P = 0.43). The percentage increase in EE (DeltaEE%; indirect calorimetry, ventilated hood) above resting EE in response to beta-AR stimulation (intravenous isoproterenol at 6, 12 and 24 ng (kg FFM)(-1) min(-1)) was greater (7.1 +/- 1.2, 13.7 +/- 1.0, 20.7 +/- 1.3 versus 5.9 +/- 0.9, 9.9 +/- 1.4, 15.9 +/- 1.70%, respectively, P = 0.04), and the dose of isoproterenol required to increase EE by 10% above resting EE was lower (8.2 +/- 1.5 versus 17.1 +/- 4.1 ng (kg FFM)(-1) min(-1), P = 0.03) in the habitually exercising adults. In contrast, vastus lateralis muscle beta(2)-AR density was similar in the habitually exercising and sedentary subjects (7.46 +/- 0.29 versus 7.44 +/- 0.60 fmol (mg dry weight muscle)(-1), P = 0.98), and was not related to DeltaEE% (r = 0.02, P = 0.94) or to the isoproterenol dose required to increase EE by 10% above resting EE (r = -0.06, P = 0.76). These findings indicate that increased beta(2)-AR density is not a mechanism contributing to the greater thermogenic responsiveness to beta-AR stimulation in adult humans who regularly perform aerobic exercise