The black population exhibits attenuated vasodilatory function across their lifespan, yet little is known regarding the mechanisms of this impairment. Recent evidence suggests a potential role for oxidative stress. Therefore, we tested the hypothesis that NADPH oxidase (NOX) and/or xanthine oxidase (XO) contribute to blunted nitric oxide (NO)-mediated cutaneous microvascular function in young black adults. In 30 white and black subjects (8 men and 7 women in each group), local heating was performed while NOX and XO were inhibited by apocynin and allopurinol, respectively, via intradermal microdialysis. The plateau in cutaneous vascular conductance (red blood cell flux/mean arterial pressure) during 39°C local heating at each site was compared with a control site perfused with lactated Ringer solution. Subsequent inhibition of NO synthase via N-nitro-l-arginine methyl ester allowed for quantification of the NO contribution to vasodilation during heating. Black individuals, relative to white individuals, had a blunted cutaneous vascular conductance plateau at the control site (45 ± 9 vs. 68 ± 13%max, P < 0.001) that was increased by both apocynin (61 ± 15%max, P < 0.001) and allopurinol (58 ± 17%max, P = 0.005). Black men and black women had similar responses to heating at the control site ( P = 0.99), yet apocynin and allopurinol increased this response only in black men (both P < 0.001 vs. control). The NO contribution was also increased via apocynin and allopurinol exclusively in black men. These findings suggest that cutaneous microvascular function is reduced because of NOX and XO activity in black men but not black women, identifying a novel sex difference in the mechanisms that contribute to blunted vascular responses in the black population. NEW & NOTEWORTHY We demonstrate that cutaneous microvascular responses to local heating are consistently reduced in otherwise healthy young black men and women relative to their white counterparts. Inhibition of NADPH oxidase and xanthine oxidase via apocynin and allopurinol, respectively, augments microvascular function in black men but not black women. These data reveal clear sex differences in the mechanisms underlying the racial disparity in cutaneous microvascular function.
Background: Central arterial stiffness is an emerging risk factor of age-related cognitive impairment and Alzheimer’s disease (AD). However, the underlying pathophysiological mechanisms remain unclear. Objective: We tested the hypothesis that carotid arterial stiffness is associated with reduced cerebral blood flow (CBF) and increased cerebrovascular resistance (CVR) in patients with amnestic mild cognitive impairment (MCI), a prodromal stage of AD. Methods: Fifty-four patients with amnestic MCI and 24 cognitively normal subjects (CN) of similar age and sex to MCI patients underwent measurements of CBF and carotid β-stiffness index using ultrasonography and applanation tonometry. Total CBF was measured as the sum of CBF from both the internal carotid and vertebral arteries, and divided by total brain tissue mass (assessed with MRI) to obtain normalized CBF (nCBF). Results: Relative to CN subjects, MCI patients showed lower nCBF (53.3 ± 3.2 vs 50.4±3.4 mL/100 g/min, P < 0.001) and higher CVR (0.143 ± 0.019 vs 0.156 ± 0.023 mmHg/mL/min, P < 0.015). Multiple linear regression analysis showed that nCBF was negatively associated with carotid β-stiffness index (B = -0.822, P < 0.001); CVR was positively associated with carotid systolic pressure (B = 0.001, P < 0.001) after adjustment for age, sex, body mass index, and MCI status. Conclusion: These findings suggest that carotid artery stiffening may contribute at least in part to the reduced nCBF and increased CVR in patients with MCI associated with augmented carotid arterial pulsatility.
Consumption of a representative fast‐food meal (FFMeal) acutely impairs peripheral conduit artery vascular function; however, the effect on cerebral vascular function remains unknown. This study tested the hypothesis that a FFMeal would impair cerebral vascular function as indexed by an attenuated increase in cerebral vascular conductance (CVCI) in the middle cerebral artery (MCA) during a hypercapnic challenge. Ten healthy men (age: 24 ± 3 years, BMI: 24.3 ± 3.8 kg/m2) were studied under two conditions; a standardized FFMeal (990 kcals, 50% fat, 36% carbohydrate, 14% protein, and 2120 mg sodium) and a fasting control condition. Basal hemodynamics, cerebral vasomotor reactivity (CVMR), and brachial artery flow‐mediated dilation (BA FMD) were completed after an overnight fast (Pre) and again 2 h and 4 h later both days. To assess CVMR, subjects rebreathed from a 5‐L bag while MCA velocity (MCAV mean) was measured using transcranial Doppler (TCD) ultrasound and converted into CVCI (MCAV mean/mean arterial pressure). Peripheral artery endothelial function was assessed via BA FMD following a standard 5‐min occlusion protocol. As expected, BA FMD was reduced at 2 h (Pre: 6.6 ± 1.7% vs. 5.2 ± 1.8%, P = 0.01). However, despite significant impairment in BA FMD, neither peak CVCI %baseline nor CVMR was affected by the FFMeal (Control–Pre: 1.9 ± 1.1, 2 h: 2.1 ± 1.1, 4 h: 1.7 ± 1.1 ∆CVCI%·∆PETCO 2 −1 vs. FFMeal–Pre: 2.1 ± 1.1, 2 h: 2.2 ± 0.7, 4 h: 1.9 ± 0.9 ∆CVCI%·∆PETCO 2 −1, time × condition P = 0.88). These results suggest that cerebral vascular reactivity to hypercapnia in healthy young men is not altered by an acute FFMeal.
In the USA, cardiovascular and cerebrovascular diseases remain more prominent in the non-Hispanic Black (BL) population relative to other racial/ethnic groups.Typically, sex differences emerge in the manifestation of these diseases, though these differences may not fully materialize in the BL population. While numerous mechanisms are implicated, differences in vascular function likely contribute. Research has demonstrated blunted vasodilatation in several vascular regions in BL versus non-Hispanic White individuals, though much of this work did not assess sex differences.Therefore, this study aimed to ascertain if indices of vascular function are different between young BL women (BW) and men (BM). Eleven BW and 15 BM (22 (4) vs. 23 (3) years) participated in this study. Each participant underwent testing for brachial artery flow-mediated dilatation (FMD), post-occlusive reactive hyperaemia and cerebral vasomotor reactivity during rebreathing-induced hypercapnia. BW exhibited greater adjusted FMD than BM (P < 0.05 for all), but similar or lower reactive hyperaemia when assessed as blood velocity (P > 0.39 for all) or blood flow reactivity (P < 0.05 for all), respectively. Across a range of hypercapnia, BW had greater middle cerebral artery blood velocity and cerebrovascular conductance index than BM (P < 0.001 for both). These preliminary data suggest that young BW have greater vascular function relative to young BM, though this was inconsistent across different indices. These findings provide insight into the divergent epidemiological findings between BM and BW. Further research is needed to elucidate possible mechanisms and relate these physiological responses to epidemiological observations.
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