The atypical antipsychotic risperidone (RSP) is often associated with weight gain and cardiometabolic side effects. The mechanisms for these adverse events are poorly understood and, undoubtedly, multifactorial in etiology. In light of growing evidence implicating the gut microbiome in the host's energy regulation and in xenobiotic metabolism, we hypothesized that RSP treatment would be associated with changes in the gut microbiome in children and adolescents. Thus, the impact of chronic (>12 months) and short-term use of RSP on the gut microbiome of pediatric psychiatrically ill male participants was examined in a cross-sectional and prospective (up to 10 months) design, respectively. Chronic treatment with RSP was associated with an increase in body mass index (BMI) and a significantly lower ratio of Bacteroidetes:Firmicutes as compared with antipsychotic-naïve psychiatric controls (ratio=0.15 vs 1.24, respectively; P<0.05). Furthermore, a longitudinal observation, beginning shortly after onset of RSP treatment, revealed a gradual decrease in the Bacteroidetes:Firmicutes ratio over the ensuing months of treatment, in association with BMI gain. Lastly, metagenomic analyses were performed based on extrapolation from 16S ribosomal RNA data using the software package, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Those data indicate that gut microbiota dominating the RSP-treated participants are enriched for pathways that have been implicated in weight gain, such as short-chain fatty acid production.

Muscle sympathetic neural activity (MSNA) influences the mechanical properties (i.e., vascular smooth muscle tone and stiffness) of peripheral arteries, but it remains controversial whether MSNA contributes to stiffness of central arteries such as the aorta and carotids. We examined whether elevated MSNA (age-related) would be independently associated with greater stiffness of central [carotid-femoral pulse wave velocity (PWV)] and peripheral (carotid-brachial PWV) arteries, in addition to lower carotid compliance coefficient (CC), in healthy men and women (n=88, age:19-73 years, 52%men). Also, we examined whether acute elevations in MSNA without increases in mean arterial pressure (MAP) using graded levels of lower body negative pressure (LBNP) would augment central and peripheral artery stiffness in young (YG, n=15, 60%men) and middle-age/older adults (MA/O, n=14, 43%men). Resting MSNA burst frequency (bursts•min −1) was significantly correlated with carotid-femoral PWV (R=0.44, P<0.001), carotid-brachial PWV (R=0.32, P=0.003), and carotid CC (R=0.28, P=0.01) after controlling for sex, MAP, heart rate, and waist-to-hip ratio (central obesity), but these correlations were abolished after further controlling for age (all P>0.05). In YG and MA/O adults, MSNA was elevated during LBNP (P<0.001) and produced significant increases in carotid-femoral PWV (YG:Δ+1.3±0.3 vs. MA/ O:Δ+1.0±0.3 m•s −1 , P=0.53) and carotid-brachial PWV (YG: Δ+0.7±0.3 vs. MA/O: Δ+0.7±0.5 m•s −1 , P=0.92), whereas carotid CC during LBNP was significantly reduced in YG but not MA/O (YG:Δ-0.04 ±0.01 vs. MA/O:Δ0.001±0.008 mm 2 •mmHg −1 , P<0.01). Collectively, these data demonstrate the influence of MSNA on central artery stiffness and its potential contribution to age-related increases in stiffness of both peripheral and central arteries.

Relative burst amplitude of muscle sympathetic nerve activity (MSNA) is an indicator of augmented sympathetic outflow and contributes to greater vasoconstrictor responses. Evidence suggests anxiety-induced augmentation of relative MSNA burst amplitude in patients with panic disorder; thus we hypothesized that acute stress would result in augmented relative MSNA burst amplitude and vasoconstriction in individuals with chronic anxiety. Eighteen participants with chronic anxiety (ANX; 8 men, 10 women, 32 ± 2 yr) and 18 healthy control subjects with low or no anxiety (CON; 8 men, 10 women, 39 ± 3 yr) were studied. Baseline MSNA and 24-h blood pressure were similar between ANX and CON ( P > 0.05); however, nocturnal systolic blood pressure % dipping was blunted among ANX ( P = 0.02). Relative MSNA burst amplitude was significantly greater among ANX compared with CON immediately preceding (anticipation) and during physiological stress [2-min cold pressor test; ANX: 73 ± 5 vs. CON: 59 ± 3% arbitrary units (AU), P = 0.03] and mental stress (4-min mental arithmetic; ANX: 65 ± 3 vs. CON: 54 ± 3% AU, P = 0.02). Increases in MSNA burst frequency, incidence, and total activity in response to stress were not augmented among ANX compared with CON ( P > 0.05), and reduction in brachial artery conductance during cold stress was similar between ANX and CON ( P = 0.92). Relative MSNA burst amplitude during mental stress was strongly correlated with state ( P < 0.01) and trait ( P = 0.01) anxiety (State-Trait Anxiety Inventory), independent of age, sex, and body mass index. Thus in response to acute stress, both mental and physiological, individuals with chronic anxiety demonstrate selective augmentation in relative MSNA burst amplitude, indicating enhanced sympathetic drive in a population with higher risk for cardiovascular disease. NEW & NOTEWORTHY Relative burst amplitude of muscle sympathetic nerve activity in response to acute mental and physiological stress is selectively augmented in individuals with chronic anxiety, which is a prevalent condition that is associated with the development of cardiovascular disease. Augmented sympathetic burst amplitude occurs with chronic anxiety in the absence of common comorbidities. These findings provide important insight into the relation between anxiety, acute stress and sympathetic activation.

No abstract

No abstract

Introduction: Nocturnal blood pressure (BP) dipping determined from 24-hour ambulatory blood pressure monitoring (ABPM) is associated with reduced cardiovascular disease (CVD) risk. Physical activity lowers the risk of CVD related, in part, to preserved endothelial function and lower aortic stiffness, however the relation between physical activity and nocturnal dipping remains unclear. The objective of our cross-sectional retrospective analysis was to assess the relation between physical activity and nocturnal BP dipping, and whether this relation was confounded by measures of vascular function. We hypothesized that higher levels of physical activity would be associated with greater nocturnal BP dipping. Methods: Healthy adults (n=172, age 19 to 65 years, 55% female) had 24-hour ABPM measured. BP recordings were taken every 30 min during the daytime and every 60 min during the nighttime. Nocturnal “dippers” had a 10-20% difference between their mean daytime and nighttime systolic BP and “non-dippers/inverse dippers” had <10% difference. The modifiable activity questionnaire was used to assess physical activity levels via self-reported days/week with greater than 30 min of moderate activity (3.0-6.0 METs) and vigorous activity (>6.0 METs). Endothelial function (brachial artery flow-mediated dilation, FMD), and aortic stiffness (carotid-femoral pulse wave velocity, cfPWV) were also assessed. Results: Nocturnal BP dippers performed more days/week of moderate and vigorous physical activity compared to non-dippers (P=0.007 and P=0.008, respectively). Both moderate (B=0.386, P=0.042) and vigorous physical activity (B=0.604, P=0.002) were associated with nocturnal BP dipping in univariate linear regression analyses. However, only vigorous activity (B=0.926, P=0.001) remained associated with nocturnal BP dipping after adjustment for age, BMI, 24-hr systolic BP and diastolic BP, brachial FMD and cfPWV. Conclusion: Vigorous physical activity may attenuate CVD risk in part from enhanced nocturnal BP dipping. Future studies should investigate additional mechanisms by which vigorous physical activity may enhance nocturnal BP dipping. This study was supported by grants from the National Institutes of Health (AG063790; HL014388, HL07121; AG043722). Dr. Pierce is supported by the Russell B. Day and Florence D. Day Endowed Chair in Liberal Arts and Sciences, University of Iowa. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Elevated short-term (24 hour) blood pressure variability (BPV) is associated with subclinical target organ damage and cardiovascular disease (CVD) among middle-aged/older (MA/O) adults with hypertension and obesity. Circulating total cholesterol (TC), low-density cholesterol (LDL-C) and triglycerides (TGs) increase with human obesity and are independent risk factors for CVD. In addition, BPV is increased in mouse models of hyperlipidemia and is normalized with statins. However, whether higher circulating lipoproteins independently contribute to greater short-term BPV among adults with obesity remains unclear. We hypothesized that higher LDL-C, TGs and lower high-density lipoprotein (HDL-C) would be associated with greater short-term BPV among individuals with obesity. Fasting plasma lipids and 24 hour ambulatory BP monitoring were assessed in fifty-six MA/O adults with obesity defined as body mass index (BMI) ≥ 30 kg/m 2 (56% F; age 54±7 yrs; BMI, 38.2±5.6 kg/m 2 ) and at least one other CVD risk factor. There was a significant relation between 24 hour systolic BPV and TC (r=0.30, P=0.03), TGs (r=0.34, P=0.01) and LDL-C (r=0.25, P=0.059), but not HDL-C (r=-0.07, P=0.61). Interestingly, these findings remained significant after adjusting for age, sex, BMI and 24 hour systolic BP (TC: r=0.34, P=0.01; TGs: r=0.39, P<0.01; LDL-C: r=0.31, P=0.03) but HDL-C remained non-significant (r=-0.16, P=0.27). In contrast, other cardiometabolic risk factors such as fasting glucose, insulin, c-reactive protein concentrations, carotid-femoral pulse wave velocity and HOMA-IR were not associated with 24 hour systolic BPV. In a multiple linear regression model that included age, sex, BMI, 24 hour systolic BP, TGs and LDL-C, only fasting TGs (β=0.02 ± 0.01, P=0.02) were a significant correlate of 24 hour systolic BPV (Model R 2 =0.24, P=0.03). Results were the same if TC was substituted for LDL-C in the model. In conclusion, higher plasma TC, LDL-C and TGs are associated with greater 24 hour BPV among MA/O adults with obesity with only TGs being independently associated with BPV. These data suggest that greater variability in BP among MA/O adults with obesity is mediated in part through circulating TGs suggesting that TGs may be a therapeutic target to modify short-term BPV.

Central arterial stiffness, a significant contributor to the development of hypertension and cardiovascular disease with aging, is linked to elevated muscle sympathetic nerve activity (MSNA) in men. However, the extent to which MSNA is associated with central arterial stiffness in women is unknown. Given that the age-related increase in MSNA and arterial blood pressure (BP) occurs at a steeper rate among women compared to men, we tested the hypothesis that resting MSNA is more strongly correlated with central arterial stiffness in women than in men. Also, because of the parallel age-related increase in MSNA, we further hypothesized that the relation between MSNA and central arterial stiffness would not be independent of age. MSNA (microneurography), aortic stiffness (carotid-femoral pulse wave velocity, CFPWV), and carotid β-stiffness (carotid tonometry and ultrasound) were assessed in 54 healthy men (n=29; 19-72 yrs; 30 ± 1 kg/m 2 ; systolic BP: 128 ± 3 mmHg) and women (n=26; 26-64 yrs; 29 ± 2 kg/m 2 ; systolic BP: 116 ± 3 mmHg). No differences between men and women were observed for CFPWV (Men: 7.0 ± 0.3 vs. Women: 6.8 ± 0.4 mmHg, P=0.747) and carotid β-stiffness (Men: 7.6 ± 0.8 vs. Women: 7.6 ± 0.5 mmHg, P=0.975). Mean BP was lower in women compared to men (Men: 93 ± 3 vs. Women: 85 ± 2 mmHg, P=0.021) and MSNA tended to be lower in women compared to men (Men: 25 ± 3 vs. Women: 20 ± 2 bursts/min, P=0.091). After adjusting for mean BP and HR (partial correlation), CFPWV was significantly correlated with MSNA in men (R=0.44, P=0.021) and women (R=0.58, P=0.004). Interestingly, further adjustment for age abolished the association between CFPWV and MSNA in men (R=0.01, P=0.968), but not in women (R=0.43, P=0.046). A moderate relation between carotid β-stiffness and MSNA was observed in men (R=0.37, P=0.063) and women (R=0.44, P=0.034), but was abolished after adjusting for age (Men: R=-0.001, P=0.995; Women: R=0.26, P=0.245). These preliminary data demonstrate that MSNA is positively correlated with central arterial stiffness in women and men independent of BP. Furthermore, abolishment of the relation between MSNA and CFPWV in men only when adjusting for age suggests that the association between MSNA and central arterial stiffness may be more robust in women.