The effect of prescription and over-the-counter medications on core temperature in adults during heat stress: a systematic review and meta-analysis.

Background: Heat stress impacts are an escalating global health concern. Public health bodies such as the World Health Organization (WHO) warn that certain medications impair thermoregulation, with limited supporting evidence. Our aim was to investigate whether medications listed by the WHO increase core temperature responses during heat stress.

Quantification and interpretation of nitric oxide-dependent cutaneous vasodilation during local heating.

Human cutaneous microdialysis approaches for assessing nitric oxide (NO)-dependent blood flow include local heating (LH) of the skin until a plateau is reached, followed by infusion of a NO synthase inhibitor such as -nitro-l-arginine methyl ester (l-NAME); however, varied methods of quantifying and expressing NO-dependent vasodilation can obfuscate data interpretation and reproducibility. We retrospectively assessed NO-dependent vasodilation during LH to 39°C or 42°C, calculated as the ) absolute contribution of the NO-dependent component (along with baseline and the non-NO-dependent component) to the total cutaneous vascular conductance (CVC) response to LH, normalized to maximal CVC (%CVC); ) difference in %CVC (Δ%CVC) between the LH plateau and post-NO synthase inhibition (l-NAME plateau; Δ%CVC = LH plateau - l-NAME plateau); ) percentage of the LH plateau attributable to Δ%CVC (%plateau = Δ%CVC/LH plateau × 100); and ) %plateau when correcting for baseline. The LH plateaus during 39°C and 42°C were 48 ± 17%CVC (9 ± 5% baseline; 2 ± 4% non-NO dependent; 36 ± 15% NO dependent) and 88 ± 10%CVC (15 ± 8% baseline; 9 ± 10% non-NO dependent; 64 ± 13% NO dependent), respectively.

Platelet aggregation response to cyclooxygenase inhibition and thromboxane receptor antagonism using impedance aggregometry: A pilot study.

Impedance aggregometry is an alternative to light transmission aggregometry that allows analysis of platelet function in whole blood samples. We hypothesized (1) impedance aggregometry would produce repeatable results, (2) inhibition of cyclooxygenase with aspirin would attenuate aggregation responses to collagen and abolish the aggregation response to arachidonic acid (AA), and (3) thromboxane receptor antagonism (terutroban) would attenuate the aggregation response to AA. Venous blood was obtained from 11 participants three times separated by at least 2 weeks.

Inhibition of nuclear factor-κB activation improves non-nitric oxide-mediated cutaneous microvascular function in reproductive-aged healthy women.

The transcriptional regulator nuclear factor-κB (NF-κB) is a mediator of endothelial dysfunction. Inhibiting NF-κB with salsalate is used to investigate inflammatory mechanisms contributing to accelerated cardiovascular disease risk. However, in the absence of disease, inhibition of NF-κB can impact redox mechanisms, resulting in paradoxically decreased endothelial function.

Financial Hardship and Age-Related Decrements in Kidney Function Among Black and White Adults in the Midlife in the United States Study.

Objective: This analysis examined if financial hardship was associated with age-related decrements in kidney function using a material-psychosocial-behavioral framework. We also tested if this association was mediated by comorbidity of cardiometabolic risk factors (obesity, elevated blood pressure, and insulin resistance).

Methods: Data from 1361 non-Hispanic Black and White adults (ages 26-94 years; non-Hispanic Black = 258) were obtained from the Wave 3 and Refresher phases of the Midlife in the United States project.

Intradermal Microdialysis: An Approach to Investigating Novel Mechanisms of Microvascular Dysfunction in Humans.

The cutaneous vasculature is an accessible tissue that can be used to assess microvascular function in humans. Intradermal microdialysis is a minimally invasive technique used to investigate mechanisms of vascular smooth muscle and endothelial function in the cutaneous circulation. This technique allows for the pharmacological dissection of the pathophysiology of microvascular endothelial dysfunction as indexed by decreased nitric oxide-mediated vasodilation, an indicator of cardiovascular disease development risk.

Nitric oxide-mediated cutaneous microvascular function is not altered in middle-aged-to-older adults following mild SARS-CoV-2 infection: A pilot study.

We tested the hypothesis that post-COVID-19 adults (PC) would have impaired cutaneous nitric oxide (NO)-mediated vasodilation compared to controls (CON). We performed a cross-sectional study including 10 (10 F/0 M, 69 ± 7 years) CON and 7 (2 F/5 M, 66 ± 8 years) PC (223 ± 154 days post-diagnosis). COVID-19 symptoms severity (survey) was assessed (0-100 scale for 18 common symptoms).

Seven days of statin treatment improves nitric-oxide mediated endothelial-dependent cutaneous microvascular function in women with endometriosis.

Introduction: Endometriosis is associated with systemic inflammation and increased risk of cardiovascular disease (CVD). Endothelial dysfunction is one of the first manifestations of CVD but is unexplored in women with endometriosis. HMG-CoA-reductase inhibitors (statins) exert potent anti-inflammatory effects, and have been proposed as an adjunctive therapy in women with endometriosis.

Skin pigmentation is negatively associated with circulating vitamin D concentration and cutaneous microvascular endothelial function.

Darkly pigmented individuals are at the greatest risk of hypovitaminosis D, which may result in microvascular endothelial dysfunction via reduced nitric oxide (NO) bioavailability and/or increased oxidative stress and inflammation. We investigated the associations among skin pigmentation (M-index; skin reflectance spectrophotometry), serum vitamin D concentration [25(OH)D], circulating inflammatory cytokine (TNF-α, IL-6, and IL-10) concentrations, and the NO contribution to local heating-induced cutaneous vasodilation (%NO-mediated vasodilation) in a diversely pigmented cohort of young adults. An intradermal microdialysis fiber was placed in the forearms of 33 healthy adults (14 men/19 women; 18-27 yr; M-index, 30-81 AU) for local delivery of pharmacological agents.

Short-term salicylate treatment improves microvascular endothelium-dependent dilation in young adults with major depressive disorder.

Reactive oxygen species (ROS)-mediated reductions in nitric oxide (NO)-dependent dilation are evident in adults with major depressive disorder (MDD); however, the upstream mechanisms remain unclear. Here, we hypothesized that nuclear factor-κB (NF-κB) activation-induced ROS production contributes to microvascular endothelial dysfunction in MDD. Thirteen treatment-naive adults with MDD (6 women; 19-23 yr) and 10 healthy nondepressed adults (HAs; 5 women; 20-25 yr) were tested before and after (open-label design) systemic NF-κB knockdown (nonacetylated salicylate; 3,000-4,500 mg/day × 4 days).

Nitric oxide-mediated cutaneous microvascular function is not altered in young adults following mild-to-moderate SARS CoV-2 infection.

Vascular dysfunction has been reported in adults who have recovered from COVID-19. To date, no studies have investigated the underlying mechanisms of persistent COVID-19-associated vascular dysfunction. Our purpose was to quantify nitric oxide (NO)-mediated vasodilation in healthy adults who have recovered from SARS-CoV-2 infection.

Acute systemic inhibition of inflammation augments endothelium-dependent dilation in women with a history of preeclamptic pregnancy.

Women who have had preeclampsia demonstrate microvascular endothelial-dysfunction, mediated in part by reduced nitric oxide (NO)-dependent dilation. Preeclamptic pregnancies are associated with elevated inflammation, and inhibition of inflammation attenuates endothelial damage in animal models of preeclampsia. However, it is unclear if inhibition of vascular inflammation improves endothelial function in women after a preeclamptic pregnancy.

Women with a history of preeclampsia have preserved sensory nerve-mediated dilatation in the cutaneous microvasculature.

New Findings: What is the central question of this study? Are sensory nerve-mediated vasodilatation and the NO-dependent contribution to that response attenuated in the cutaneous microvasculature of women who have had preeclampsia? What is the main finding and its importance? Women who have had preeclampsia demonstrate attenuated microvascular endothelium-dependent dilatation compared to women with a history of uncomplicated pregnancy. However, there are no differences in sensory nerve-mediated vasodilatation between groups. This suggests that the neurogenic response is not altered following preeclampsia, and that the NO-dependent vasodilatation of the neurogenic response is not related to endothelium-dependent NO-mediated dilatation in these women.

Menthol-induced activation of TRPM8 receptors increases cutaneous blood flow across the dermatome.

Topical menthol-based analgesics increase skin blood flow (SkBF) through transient receptor potential melastatin 8 (TRPM8) receptor-dependent activation of sensory nerves and endothelium-derived hyperpolarization factors. It is unclear if menthol-induced TRPM8 activation mediates a reflex change in SkBF across the dermatome in an area not directly treated with menthol. The purpose of this study was to determine the effects of localized topical menthol application on SkBF across a common dermatome.

Vascular Health Triad in Humans With Hypertension-Not the Usual Suspects.

Hypertension (HTN) affects more than one-third of the US population and remains the top risk factor for the development of cardiovascular disease (CVD). Identifying the underlying mechanisms for developing HTN are of critical importance because the risk of developing CVD doubles with ∼20 mmHg increase in systolic blood pressure (BP). Endothelial dysfunction, especially in the resistance arteries, is the primary site for initiation of sub-clinical HTN.

Hydrogen sulfide-dependent microvascular vasodilation is improved following chronic sulfhydryl-donating antihypertensive pharmacotherapy in adults with hypertension.

Hypertension is characterized by systemic microvascular endothelial dysfunction, in part due to a functional absence of hydrogen sulfide (HS)-mediated endothelium-dependent dilation. Treatment with a sulfhydryl-donating ACE inhibitor (SH-ACE inhibitor) improves endothelial function in preclinical models of hypertension. To date, no studies have directly assessed the effects of SH-ACE-inhibitor treatment on HS-dependent vasodilation in humans with hypertension.

Skeleton-secreted PDGF-BB mediates arterial stiffening.

Evidence links osteoporosis and cardiovascular disease but the cellular and molecular mechanisms are unclear. Here we identify skeleton-secreted platelet-derived growth factor-BB (PDGF-BB) as a key mediator of arterial stiffening in response to aging and metabolic stress. Aged mice and those fed high-fat diet (HFD), relative to young mice and those fed normal chow food diet, respectively, had higher serum PDGF-BB and developed bone loss and arterial stiffening.

Temperature regulation during exercise in the heat: Insights for the aging athlete.

Objective: The purpose of this review is to evaluate the currently-available literature regarding the impact of both primary aging and age-related fitness on thermoregulatory function during exercise in the heat. In so doing, we aim to (1) characterize the influence of fitness in mitigating age-related declines in thermoregulation, (2) address the limitations of prior experimental approaches for investigating age-related thermoregulatory impairments, (3) examine to what extent aerobic fitness can be maintained in the aging athlete, and (4) begin to address the specific environmental conditions in which age-related impairments in thermoregulatory function may place highly active older adults at increased risk for heat-related illness and injury and/or limited performance.

Design: Mini-review.

Reproducibility of the neurocardiovascular responses to common laboratory-based sympathoexcitatory stimuli in young adults.

The magnitude of blood pressure (BP) and muscle sympathetic nerve activity (MSNA) responses to laboratory stressors is commonly used to compare neurocardiovascular responsiveness between groups and conditions. However, no studies have rigorously examined the reproducibility of BP and MSNA responsiveness. Here, we assess the within-visit reproducibility of BP (finger photoplethysmography) and MSNA (microneurography) responses to isometric handgrip (HG) and postexercise ischemia (PEI) in young healthy adults ( = 30).

Four weeks of vitamin D supplementation improves nitric oxide-mediated microvascular function in college-aged African Americans.

Reduced nitric oxide (NO)-mediated cutaneous vasodilation, secondary to increased oxidative stress, presents in young African American (AA) compared with European American (EA) adults and may be modulated by vitamin D status. We assessed cutaneous microvascular function in 18 young, healthy (21 ± 2 yr; 9 men, 9 women) subjects before (pre, 8 AA, 10 EA) 4 wk of 2,000 IU/day oral vitamin D supplementation and in 13 subjects after (post, 7 AA, 6 EA) 4 wk of 2,000 IU/day oral vitamin D supplementation. Serum vitamin D concentrations [25(OH)D] were measured at each visit.

AHA/ACC-defined stage 1 hypertensive adults do not display cutaneous microvascular endothelial dysfunction.

In 2017, the American Heart Association (AHA) and American College of Cardiology (ACC) redefined stage 1 hypertension to systolic blood pressure (BP) 130-139 mmHg or diastolic BP 80-89 mmHg; however, the degree to which microvascular endothelial dysfunction is evident in adults with stage 1 hypertension remains equivocal. We tested the hypotheses that cutaneous microvascular endothelial dysfunction would be present in adults with stage 1 hypertension (HTN1) compared with normotensive adults (NTN; BP <120/<80 mmHg) but would be less severe compared with adults with stage 2 hypertension (HTN2; systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg) and that this graded impairment would be mediated by reductions in nitric oxide (NO)-dependent dilation. This retrospective analysis included 20 NTN (5 men; 45-64 yr; BP 94-114/60-70 mmHg), 22 HTN1 (11 men; 40-74 yr; BP 110-134/70-88 mmHg), and 44 HTN2 (27 men; 40-74 yr; BP 128-180/80-110 mmHg).

Childhood socioeconomic status, comorbidity of chronic kidney disease risk factors, and kidney function among adults in the midlife in the United States (MIDUS) study.

Background: There is a lack of empirical effort that systematically investigates the clustering of comorbidity among known risk factors (obesity, hypertension, diabetes, hypercholesterolemia, and elevated inflammation) of chronic kidney disease (CKD) and how different types of comorbidity may link differently to kidney function among healthy adult samples. This study modeled the clustering of comorbidity among risk factors, examined the association between the clustering of risk factors and kidney function, and tested whether the clustering of risk factors was associated with childhood SES.

Methods: The data were from 2118 participants (ages 25-84) in the Midlife in the United States (MIDUS) Study.