bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of intranasal insulin on muscle sympathetic nerve activity and peripheral vascular conductance in healthy young adults
Authors: McMillan Neil , Shariffi Brian , Jacob Dain , Harper Jennifer , Manrique-Acevedo Camilla , Padilla Jaume , Limberg Jacqueline 
Published: May 2023

Objective: Systemic insulin increases muscle sympathetic nervous system activity (MSNA) via both central actions within the brainstem and peripheral activation of the arterial baroreflex. Augmented MSNA during hyperinsulinemia likely restrains peripheral vasodilation and contributes to the maintenance of blood pressure (BP). However, in the absence of insulin action within the peripheral vasculature, whether increased MSNA with insulin stimulation promotes vasoconstriction and increased BP remains unknown. Herein, using intranasal administration of insulin, we examined for the first time central actions of insulin on MSNA, as well as peripheral hemodynamic effects in healthy humans. We hypothesized intranasal insulin would increase MSNA and promote peripheral vasoconstriction and an increase in BP in healthy young adults. Methods: Twenty healthy young adults were randomized into time control [n=13 (5F/8M), 28±1 yrs] or 160 IU of intranasal insulin administered over 5 minutes [n=7 (0F/7M), 27±3 yrs]. MSNA (peroneal microneurography), BP (finger photoplethysmography), and leg blood flow (LBF, femoral Doppler ultrasound) data are reported from baseline and 15 minutes following insulin administration. Leg vascular conductance (LVC = LBF ÷ mean BP x 100) was calculated. Results: Following intranasal administration, MSNA (26±2 to 31±2 bursts/min, p=0.02; n=4) and mean BP (93±2 to 98±3 mmHg, p=0.02) increased while LVC tended to decrease (106±7 to 99±7 mL/min/100 mmHg, p=0.063). Venous systemic insulin and plasma glucose remained unchanged throughout the protocol (p>0.05). During time control experiments, MSNA (25±2 to 25±1 bursts/min, p=0.72; n=9), mean BP (92±2 to 93±2 mmHg, p=0.50), and LVC (80±8 to 81±9 mL/min/100 mmHg, p=0.58) did not differ from baseline. Conclusions: We provide the first evidence that intranasal insulin administration in healthy young adults acutely increases MSNA to promote peripheral vasoconstriction and an increase in BP. These preliminary results have important implications for our understanding of cardiovascular control mechanisms during hyperinsulinemia and provide the opportunity to extend these findings to disease states (e.g., insulin resistance, diabetes) in future studies. Funding: CAFNR Joy of Discovery (JKL, JP) 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.
B1-adrenergic blockers provide cardiac protection through extracellular traps inhibition during widespread inflammation
Authors: Mansart Arnaud , Adam Lucille , Gasser Adeline , Bourcier Camille , Vinit Stephane , Annane Djillali 
Published: May 2023

Sepsis is one of the leading causes of death worldwide, and no therapy is available other than intensive care treatments. Drug development attempts have mainly focused on controlling inflammation or treating dysfunction, without significant improvement in the last decades. Recently, interest has emerged in β1-adrenergic blockade, which has proved beneficial to both parameters. Unfortunately, the specific underlying mechanisms have not been addressed yet. Our study aimed to investigate on mice (adult Swiss male, 30-45g) lipopolyssacharide or cecal ligature and puncture models the effects of atenolol, a β1-adrenergic blocker, currently used in intensive care units for hypertension and arrhythmia. The results demonstrated a beneficial effect of treatment on survival and a preservation of cardiac function including left ventricular ejection fraction (33±2,8% in sepsis group versus 55±5,1% in sepsis-treated group, p<0,05) at a concentration reducing heart rate by approximately 10%.We wondered if beneficial results obtained with atenolol could be due to a modulation of extracellular traps. These components are essential in pathogen spreading control and are increased during sepsis. However, an excess of their production induces vascular occlusions and acute heart injuries.We demonstrated that neutrophils extracellular traps were increased in heart and blood during sepsis and decreased significantly following atenolol administration (blood: 1.1±0,3% in control group, 13,4±1.8% in sepsis group, 6.9±1.2% in sepsis-treated group). This beneficial effect of atenolol was not associated with other modulations of neutrophil function such as their ability to phagocyte (33,6±3,9% in sepsis group versus 25.6±3.6% in sepsis-treated group, p>0,05), to undergo apoptosis (Annexin V+/ L/D-: 13,2±2.1% in sepsis group versus 14.1±2.9% in sepsis-treated group, p>0,05) or to degranulate. Blood neutrophil phenotypes associated with their maturation state (expression of CD62L and CXCR2) or ability to migrate into tissue (expression of adhesion molecules PSGL1, LFA1, VLA4, PECAM1) was also similar between LPS and LPS-treated groups. Although, the modulation of extracellular traps production by atenolol was also observed in other immune cells population able to extrude chromatin fibers in extracellular space such as macrophages. These results suggest a specific beneficial effect of ß1-adrenergic blockers on extracellular traps formation associated with cardiac function preservation and ultimately survival without detrimental effect on heart rate during widespread inflammation. This work was supported by funding from INSERM and Paris-Saclay University-UVSQ. 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.
Cerebral Hemodynamics Comparison between Transcranial Doppler Ultrasound and 4D Flow MRI
Authors: Fico Brandon , Miller Kathleen , Rivera-Rivera Leonardo , Corkery Adam , Pearson Andrew , Loggie Nicole , Howery Anna , Rowley Howard , Johnson Kevin , Johnson Sterling , Weiben Oliver , Barnes Jill 
Published: May 2023

Age-related changes in cerebral hemodynamics are controversial and discrepancies may be due to experimental techniques. As such, the purpose of this study was to compare cerebral hemodynamics measurements of the middle cerebral artery (MCA) between transcranial Doppler ultrasound (TCD) and four-dimensional flow MRI (4D flow MRI). Twenty young (25 ± 3 years) and 19 older (62 ± 6 years) participants underwent two randomized study visits to evaluate hemodynamics at baseline (normocapnia) and in response to stepped hypercapnia (4% CO2, and 6% CO2) using TCD and 4D flow MRI. Cerebral hemodynamics measures included MCA velocity, MCA flow, cerebral pulsatility index (PI) and cerebrovascular reactivity. Cerebrovascular reactivity was calculated as the linear relationship between cerebrovascular conductance (CVC using 4D flow MRI) or cerebrovascular conductance index (CVCi using TCD) and changes in ETCO2 at rest and during hypercapnia. MCA velocity between the methods was positively correlated across the conditions (r=0.262; p=0.004). Additionally, cerebral PI of the MCA was significantly correlated between TCD and 4D flow MRI across the conditions (r=0.236; p=0.010). However, there was no association between MCA velocity using TCD and MCA flow using 4D flow MRI across the conditions (r=0.079; p=0.397). When age-associated differences in cerebrovascular reactivity were compared using both methodologies, cerebrovascular reactivity was greater in young adults compared to older adults when using 4D flow MRI (2.11±1.68 ml/min/mmHg/mmHg vs. 0.78±1.68 ml/min/mmHg/mmHg; p=0.019), but not with TCD (0.88±1.01 cm/s/mmHg2 vs. 0.68±0.94 cm/s/mmHg2; p=0.513). In conclusion, our results demonstrated good agreement between the methods measuring MCA velocity at normocapnia and in response to hypercapnia, but MCA velocity with TCD and MCA flow with MRI were not related. In addition, measurements using 4D flow MRI revealed additional effects of aging on cerebral hemodynamics that were not apparent using TCD. This study was funded by the NIH grants (HL118154, NS117746), the NIH, Ruth L. Kirschstein National Research Service Award T32's from the National Institute on Aging to the University of Wisconsin-Madison Biology of Aging & Age-Related Diseases (AG000213) and the National Heart Lung and Blood Institute to the University of Wisconsin-Madison Cardiovascular Research Center (HL007936) as well as the Wisconsin Alumni Research Foundation. This study was also supported by Alzheimer's Association Research Fellowship (AARF-22-924325). 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.
Effect of Central Chemoreceptors on the Peripheral Chemoreflex Response to Hypoxia
Authors: Guluzade Nasimi , Huggard Joshua , Duffin James , Keir Daniel 
Published: May 2023

In the absence of central chemoreceptor input, the slope of the hypoxic ventilatory response (HVR) to progressive oxyhemoglobin desaturation (L·min-1·mmHg-1·%SaO2-1) – a measure of peripheral chemoreflex sensitivity – increases linearly with carbon dioxide tension (PCO2). We assessed whether this relationship remains linear with increasing central PCO2 in humans. Over four days, 20 participants (10 females; mean±SD age: 24±4 years) completed three repetitions of modified rebreathing with end-tidal PO2 (PETO2) clamped at 150, 70, 60, and 45 mmHg. End-tidal PCO2 (PETCO2), PETO2, ventilation (V̇E), and SaO2 were measured breath-by-breath by dual gas analyser, pneumotach, and pulse oximetry. The V̇E vs PETCO2 relationship in the hyperoxic test gave the central chemoreflex response to PCO2 and the hypoxic tests provided a combined central-peripheral chemoreflex response. The V̇E vs PETCO2 relationship of repeated trials were linear-interpolated, combined, averaged into 1 mmHg bins, and fit with a linear function (V̇ES, L·min-1·mmHg-1) to provide hyperoxic and hypoxic profiles. HVR was computed at 1 mmHg intervals of PETCO2 as follows: the difference in V̇E between the three hypoxic profiles and the hyperoxic profile (ΔV̇E) was calculated; these three ΔV̇E values were plotted against their corresponding SaO2; and linear regression determined HVR (L·min-1·mmHg-1·%SaO2-1). Steps were repeated at each PETCO2 to produce the HVR vs PCO2 relationship. Each participant’s HVR vs PETCO2 relationship was fit with a linear and polynomial function and Akaike Information Criterion identified the best-fit model. One-way repeated measures analysis of variance assessed between-condition differences. V̇ES rose (p<0.001) with isoxic PO2 from 3.7±1.5 L·min-1·mmHg-1 at 150 mmHg to 4.4±1.8, 5.0±1.6, and 6.0±2.2 L·min-1·mmHg-1 at 70, 60, and 45 mmHg, respectively. Mean SaO2 fell progressively (99.3%, 93.7%, 90.4%, and 80.5% for 150, 70, 60, and 45 mmHg, respectively; p<0.001). In all individuals, HVR increased with PETCO2 and this relationship was best described by a linear model in 75% of participants. In most participants, the peripheral chemoreflex-mediated HVR maintained a linear relationship with PETCO2 despite increasing central chemoreflex activation. Data suggest that central chemoreceptors did not alter the peripheral chemoreflex response to low O2. Natural Sciences and Engineering Research Council of Canada 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.
Renal denervation mitigates renal dysfunction in a rat model of tacrolimus-induced nephrotoxicity
Authors: Dayton Alex , Lauar Mariana , Ross Jaryd , Evans Louise , Osborn John 
Published: May 2023

Tacrolimus, a macrolide calcineurin inhibitor, is the most widely used immune suppressant medication after solid-organ transplant in humans, however, its use is complicated by nephrotoxicity and the development of chronic kidney disease. Interestingly, transplanted kidneys, which lack renal nerves, enjoy a relative protection from tacrolimus-induced nephrotoxicity. Consistent with this clinical observation, we explored the hypothesis that renal denervation would protect against the development of kidney disease in a rat model of tacrolimus-induced nephrotoxicity.To test this hypothesis, Sprague-Dawley rats underwent either total renal denervation (TRDN) or sham denervation and thereafter were injected with either vehicle (corn oil) or tacrolimus (2 mg/kg) for 14 days. At the end of this protocol plasma blood urea nitrogen (BUN), a marker of renal filtration function, was substantially lower in TRDN rats treated with tacrolimus than in their sham counterparts (24 vs 36 mg/dL, respectively). Similarly, TRDN rats treated with tacrolimus demonstrated substantially less renal fibrosis and glomerular damage than their sham counterparts as demonstrated by trichrome staining and PAS staining.Together our results demonstrate that total renal denervation is protective against the development of tacrolimus-induced nephrotoxicity. This finding suggests that renal denervation of the kidneys of solid-organ transplant recipients could substantially decrease the burden of chronic kidney disease in the transplant population. R01 HL116476. T32HL144472. 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.
17 Beta-estradiol is associated with increased cardiovascular risk in the castrated male rat
Authors: Mallette Jordan , Oudomrath Speyrer Adrian , Crudup Breland , Rawls Adam , Cockrell Kathy , Willis Alex , Davenport Kacey , Yanes Cardozo Licy , Shawky Noha , Alexander Barbara 
Published: May 2023

Gender affirming hormone therapy (GAHT) is used in individuals born one gender but identify as a different gender. For the male-to-female transition, GAHT includes 17β-estradiol (E2) plus either an anti-androgen (AA) or surgical intervention, castration (CTX). We hypothesize that GAHT will increase cardiovascular risk in the transfemale. Methods: Male Sprague Dawley rats were randomly assigned to the following groups: Control, E2 [5 mg/day, silastic capsule pellet s.c., replaced every 3 weeks], AA [Spironolactone, 10 ng/kg/day, diet], CTX, E2+AA, and E2+CTX. AA and E2 were initiated at 14 weeks of age; CTX were exposed to AA for 2 weeks prior to CTX at 16 weeks of age. Each group was subdivided into EchoMRI for measurement of lean and fat mass and serial E2 (ELISA) (N=6-8) up to 27 weeks of age, or implanted with radiotelemetry (N=4-5) inserted at 16 weeks for continuous measurement of blood pressure (BP) starting at 18 weeks to 27 weeks of age. Angiotensin (ANG) II (200 ng/kg/min, s.c. minipumps) was started at 24 weeks of age and continued for 3 weeks in the blood pressure group. Statistics: One-way ANOVA with multi-group comparisons, P<0.05 was considered significant. Results: Average testes weight was reduced in E2-treated male rats compared to Control, P<0.0001 (1.9±0.04, 0.3±0.02, 1.9±0.05, 0.3± 0.01 grams; Control, E2, AA, E2+AA, respectively). Body weight (374±5, 287±5, 390±2, 392±11, 303±8, 287±10 grams) and lean body mass (338±4, 254±5, 351±3, 350±10, 266±7, 262±6 grams) were decreased in E2-treated male rats compared to Control, P<0.005, Control, E2, AA, CTX, E2+AA, E2+CTX, respectively. E2 administration was associated with a significant increase in circulating E2 in E2-treated male rats versus Control, P<0.0001 (21±5, 367±37, 10±1, 19±5, 415±35, 359±41 pg/ml; Control, E2, AA, CTX, E2+AA, E2+CTX, respectively). The BP response to ANG II was elevated in Control, E2, AA, and E2+CTX, but not in CTX or E2+AA. These data indicate protection from ANG II hypertension was abolished with E2 in CTX male rats, but the BP response to ANG II was attenuated in CTX and E2+AA. Collectively, these studies indicate that E2 enhances cardiovascular risk in CTX male rats and highlights the importance of sex steroids on BP control. HL143459, P20-GM-104357, P20-GM121334, T32-HL105324, LGBTQ Fund of MS 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.
Effects of bioidentical hormone therapy on endothelial function and blood pressure
Authors: Schwab Allyson , Del Vecchio Angelica , Welti Laura , Johnson Ericka , Haigh Katherine , Wenner Megan 
Published: May 2023

BACKGROUND: Traditional hormone therapy (HT) is effective for managing menopausal symptoms. Although controversial, HT may also have cardioprotective effects, such as improving endothelial function. However, HT usage plummeted following the Women’s Health Initiative. A popular therapeutic option that has emerged as an alternative is bioidentical hormone therapy (bioHT). Although popular for its claim of being a natural therapy, the effects of bioHT on the cardiovascular system, specifically endothelial function and blood pressure, are not well established in menopausal women. PURPOSE: To test the hypothesis that 5 weeks of bioHT will improve endothelial function and blood pressure in menopausal women. METHODS: Women were recruited from the local community and clinics offering bioHT. Women seeking bioHT completed baseline testing (pre) within seven days of pellet insertion, and again after 5 weeks of treatment (post). Control women were not using any form of hormones, and measured at their convenience 5 weeks apart. Endothelial function was measured using brachial artery flow mediated dilation (FMD). Resting brachial blood pressure was recorded in triplicate in the supine position using an automated sphygmomanometer (Dinamap Dash 2000). Comparisons were made using two-way repeated measures ANOVA. RESULTS: Eleven women completed the study: 4 bioHT (57 ± 5 yrs) and 7 Control (54+4 yrs). Women were well matched for body mass index (bioHT: 25+3 kg/m2; control: 24+3 kg/m2; p=0.75), total cholesterol (bioHT: 213+71mg/dL; control 206+46mg/dL, p=0.84), and fasting plasma glucose (bioHT: 89+6mg/dL; control 90+13mg/dL, p=0.83). After 5 weeks, FMD did not change in bioHT (pre: 4.89% ± .8; post: 5.76% ± 2.2) or control women (pre: 3.73% ± 1.3; post: 4.18% ± 1.7; p>0.10). Resting systolic blood pressure was also not different after 5 weeks in bioHT (pre: 132 ± 20mmHg, post: 126 ± 17mmHg) or control women (pre: 113 ± 5mmHg, post: 110 ± 9mmHg; p>0.05). However, resting diastolic blood pressure tended to decrease in bioHT (pre: 79 ± 12mmHg, post: 72 ± 11mmHg; p=0.08) but not control women (pre: 71 ± 5 mmHg, post: 70 ± 7mmHg; p=0.52). CONCLUSION: These preliminary findings suggest that 5 weeks of bioHT does not negatively impact endothelial function, and may lower resting blood pressure. Additional data are needed to further assess the implications of bioHT on the cardiovascular system. Supported by NIH R01 HL 146558 and P20 GM113125 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.
Impaired Endothelial Vasomotor Function with Borderline-High Triglycerides
Authors: Garcia Vinicius , Dow Caitlin , Greiner Jared , Diehl Kyle , Stauffer Brian , DeSouza Christopher 
Published: May 2023

Approximately 1 in 3 adults in the United States have a triglyceride (TG) concentration above 150 mg/dL and 1 in 5 adults have TG levels 200 mg/dL or higher. Moreover, the prevalence of suboptimal TGs (>150 mg/dL) has increased 5-fold in middle-aged and older adults over the last 3 decades. While much attention has focused on the cardiovascular effects of high and very high TG levels, where other lipid and metabolic abnormalities are often present, there are currently little data on the influence of borderline-high TG concentrations on vascular health. This represents a critical void in our understanding of the pathogenesis of cardiovascular disease (CVD) with TGs. Impaired endothelial vasomotor function is a central etiologic feature in the development of CVD and associated thrombotic events. We tested the hypothesis that endothelium-dependent vasomotor function is impaired in adults with borderline-high TG concentrations. Thirty-two sedentary, adults were studied: 15 (7M/8F, age: 56±1 yr; BMI: 26.8±0.6 kg/m2) with normal TG (35-140 mg/dL) and 17 (9M/8F, age: 57±1 yr; BMI: 28.7±0.8 kg/m2) with borderline-high TG (150-199 mg/dL) levels. Forearm blood flow (FBF; plethysmography) was determined in response to the intra-arterial infusion: acetylcholine (ACh) (4.0, 8.0, and 16.0 mg/100 mL tissue/min), sodium nitroprusside (1.0, 2.0, and 4.0 mg/100 mL tissue/min) and selective ETa receptor blocker (BQ-123, 100 nmol/min for 60 min). FBF response to ACh was significantly lower (~20%) in the borderline-high TG (from 4.7±0.3 to 11.6+0.6 mL/100 mL tissue/min) vs normal TG (from 4.3±0.3 to 14.6±0.5 mL/100 mL tissue/min) group. There were no significant group differences in the FBF responses to sodium nitroprusside. BQ-123 elicited a significant vasodilator response (~20%) in the borderline-high TG adults but did not alter FBF in the normal TG adults. Co-infusion of BQ-123 did not affect FBF responses to ACh in normal TG group but resulted in an ~30% increase in Ach-induced vasodilation (from 4.3±0.4 to 15.1±0.7 mL/100 mL tissue/min; P<0.05) in borderline-high TG group. Triglyceride levels were significantly and inversely associated with total FBF response to ACh (r=-0.63) and positively associated with the peak FBF response to BQ-123 (r=0.53; P<0.05). These results indicate that borderline-high TG concentrations are associated with diminished endothelium-dependent vasodilation and enhanced ET-1-mediated vasoconstrictor tone. Impaired endothelial vasomotor function may underlie the increased risk of CVD in adults with borderline-high TG levels. Nothing to disclose 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.