scholarly journals Sex differences in the mechanisms mediating blunted cutaneous microvascular function in young black men and women

2018 ◽  
Vol 315 (4) ◽  
pp. H1063-H1071 ◽  
Author(s):  
Jordan C. Patik ◽  
Bryon M. Curtis ◽  
Aida Nasirian ◽  
Jennifer R. Vranish ◽  
Paul J. Fadel ◽  
...  

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 Nω-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.

2014 ◽  
Vol 117 (3) ◽  
pp. 277-283 ◽  
Author(s):  
Patricia J. Choi ◽  
Vienna E. Brunt ◽  
Naoto Fujii ◽  
Christopher T. Minson

Cutaneous hyperemia in response to rapid skin local heating to 42°C has been used extensively to assess microvascular function. However, the response is dependent on both nitric oxide (NO) and endothelial-derived hyperpolarizing factors (EDHFs), and increases cutaneous vascular conductance (CVC) to ∼90–95% maximum in healthy subjects, preventing the study of potential means to improve cutaneous function. We sought to identify an improved protocol for isolating NO-dependent dilation. We compared nine heating protocols (combinations of three target temperatures: 36°C, 39°C, and 42°C, and three rates of heating: 0.1°C/s, 0.1°C/10 s, 0.1°C/min) in order to select two protocols to study in more depth ( protocol 1; N = 6). Then, CVC was measured at four microdialysis sites receiving: 1) lactated Ringer solution (Control), 2) 50-mM tetraethylammonium (TEA) to inhibit EDHFs, 3) 20-mM nitro-L-arginine methyl ester (L-NAME) to inhibit NO synthase, and 4) TEA+L-NAME, in response to local heating either to 39°C at 0.1°C/s ( protocol 2; N = 10) or 42°C at 0.1°C/min ( protocol 3; N = 8). Rapid heating to 39°C increased CVC to 43.1 ± 5.2%CVCmax (Control), which was attenuated by L-NAME (11.4 ± 2.8%CVCmax; P < 0.001) such that 82.8 ± 4.2% of the plateau was attributable to NO. During gradual heating, 81.5 ± 3.3% of vasodilation was attributable to NO at 40°C, but at 42°C only 32.7 ± 7.8% of vasodilation was attributable to NO. TEA+L-NAME attenuated CVC beyond L-NAME at temperatures >40°C (43.4 ± 4.5%CVCmax at 42°C, P < 0.001 vs. L-NAME), suggesting a role of EDHFs at higher temperatures. Our findings suggest local heating to 39°C offers an improved approach for isolating NO-dependent dilation and/or assessing perturbations that may improve microvascular function.


Author(s):  
John D. Akins ◽  
Rauchelle E. Richey ◽  
Jeremiah C. Campbell ◽  
Zachary T. Martin ◽  
Guillermo Olvera ◽  
...  

Non-Hispanic black (BL) individuals have the greatest prevalence of cardiovascular disease (CVD), relative to other racial/ethnic groups (e.g., non-Hispanic white population; WH) which may be secondary to blunted vascular function. While women typically present with reduced CVD relative to men of the same racial/ethnic group, the prevalence is similar between BL women and men though the mechanisms differ. This study hypothesized that reduced microvascular function in young, BL women is associated with endothelin-1 (ET-1) overactivity or insufficient L-arginine bioavailability. Nine BL and 9 WH women participated (age: 20 ± 2 vs. 22 ± 2 y). Cutaneous microvascular function was assessed during 39°C local heating, while Lactated Ringer's (control), BQ-123 (ET-1 receptor type A antagonist), BQ-788 (ET-1 receptor type B antagonist), or L-arginine was infused via intradermal microdialysis to modify cutaneous vascular conductance (CVC). Subsequent infusion of Nω-nitro-L-arginine methyl ester allowed for quantification of the nitric oxide (NO) contribution to vasodilation, while combined sodium nitroprusside and 43°C heating allowed for normalization to maximal CVC (%CVCmax). BL women had blunted %CVCmax and NO contribution to dilation during the 39°C plateau (P < 0.027 for both). BQ-123 improved thisresponse through augmented NO-mediated dilation (P < 0.048 for both). BQ-788 and L-arginine, did not alter the CVC responses (P > 0.835 for both) or the NO contribution (P > 0.371 for both). Cutaneous microvascular function is reduced in BL women, and ET-1 receptor type A may contribute to this reduced function. Further research is needed to better characterize these mechanisms in young, BL women.


1985 ◽  
Vol 56 (2) ◽  
pp. 547-555E ◽  
Author(s):  
Pamela Trotman Reid ◽  
W. La Vome Robinson

Family background and personality characteristics of black professionals who held doctorates were examined for possible commonalities and sex differences. 30 black men and 34 black women from a variety of professional fields participated in this mail survey which included demographic items and personality scales. The majority of the sample had educated mothers who were employed during their childhood. In addition, the professionals held traditional religious affiliations, had small numbers of children, and their spouses typically were college graduates. The professionals were highly motivated and self-oriented individuals who were tolerant of differences in moral and personal values. Women were even less conventional than men. The women were likely to be unmarried and childless; they also had parents with more education. In general, however, with respect to personality measures, few differences existed between the men and women.


2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Jennifer C. Harvey ◽  
Bruno T. Roseguini ◽  
Benjamin M. Goerger ◽  
Elizabeth A. Fallon ◽  
Brett J. Wong

We tested the hypothesis that a high fat meal (HFM) would impair cutaneous vasodilation, while thermotherapy (TT) would reverse the detrimental effects. Eight participants were instrumented with skin heaters and laser-Doppler (LD) probes and tested in three trials: control, HFM, and HFM + TT. Participants wore a water-perfused suit perfused with 33°C (control and HFM) or 50°C (HFM + TT) water. Participants consumed 1 g fat/kg body weight. Blood samples were taken at baseline and two hours post-HFM. Blood pressure was measured every 5–10 minutes. Microvascular function was assessed via skin local heating from 33°C to 39°C two hours after HFM. Cutaneous vascular conductance (CVC) was calculated and normalized to maximal vasodilation (%CVCmax). HFM had no effect on initial peak (48 ± 4 %CVCmax) compared to control (49 ± 4 %CVCmax) but attenuated the plateau (51 ± 4 %CVCmax) compared to control (63 ± 4 %CVCmax,P< 0.001). Initial peak was augmented in HFM + TT (66 ± 4 %CVCmax) compared to control and HFM (P< 0.05), while plateau (73 ± 3 %CVCmax) was augmented only compared to the HFM trial (P< 0.001). These data suggest that HFM negatively affects cutaneous vasodilation but can be minimized by TT.


Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Albert Liu ◽  
Mehul D Patel ◽  
Alden L Gross ◽  
Thomas Mosley ◽  
Andreea Rawlings ◽  
...  

Background: The effect of retirement on cognitive functioning is not clear. We examined the association between age at retirement, midlife occupation, and cognitive decline in the large Atherosclerosis Risk in Communities (ARIC) biracial community-based cohort. Methods: Retirement status after ARIC visit 4 (1996-98) was reported in annual follow-up questionnaires administered in 1999-2007 (n= 8,426), and classified as occurring before or after age 70. Current or most recent occupation at visit 1 (1987-89) was categorized based on 1980 US census major occupation groups and tertiles of Nam-Powers-Boyd occupational status score (a measure of socioeconomic status of occupations, hereby used as a proxy for occupational complexity). Generalized estimating equation models were used to examine the associations of retirement with trajectories of a global cognitive factor score, assessed in 1990-92 (visit 2), 1996-98 (visit 4) and 2011-2013 (visit 5). Models were a priori stratified by race and sex and adjusted for demographics and comorbidities. To account for attrition, we also performed multiple imputation by chained equations. Results: Retirement before age 70 is associated with higher educational level and higher occupational status score in white men and women, and in black men. We observed associations between retirement before age 70 and lower baseline cognitive scores, as well as slower cognitive decline in white men and women, and in black men (Figure). The results did not change substantially after adjusting for the occupational status score or accounting for attrition. Conclusion: Retirement before age 70 was significantly associated with lower baseline cognitive scores and slower cognitive decline in whites and in black men. The lack of similar associations in black women and the investigation of reasons for the observed associations warrant further research.


Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Monika M Safford ◽  
Paul Muntner ◽  
Raegan Durant ◽  
Stephen Glasser ◽  
Christopher Gamboa ◽  
...  

Introduction: To identify potential targets for eliminating disparities in cardiovascular disease outcomes, we examined race-sex differences in awareness, treatment and control of hyperlipidemia in the REGARDS cohort. Methods: REGARDS recruited 30,239 blacks and whites aged ≥45 residing in the 48 continental US between 2003-7. Baseline data were collected via telephone interviews followed by in-home visits. We categorized participants into coronary heart disease (CHD) risk groups (CHD or risk equivalent [highest risk]; Framingham Coronary Risk Score [FRS] >20%; FRS 10-20%; FRS <10%) following the 3 rd Adult Treatment Panel. Prevalence, awareness, treatment and control of hyperlipidemia were described across risk categories and race-sex groups. Multivariable models examined associations for hyperlipidemia awareness, treatment and control between race-sex groups compared with white men, adjusting for predisposing, enabling and need factors. Results: There were 11,677 individuals at highest risk, 847 with FRS >20%, 5791 with FRS 10-20%, and 10,900 with FRS<10%; 43% of white men, 29% of white women, 49% of black men and 43% of black women were in the highest risk category. More high risk whites than blacks were aware of their hyperlipidemia but treatment was 10-17% less common and control was 5-49% less common among race-sex groups compared with white men across risk categories. After multivariable adjustment, all race-sex groups relative to white men were significantly less likely to be treated or controlled, with the greatest differences for black women vs. white men (Table). Results were similar when stratified on CHD risk and area-level poverty tertile. Conclusion: Compared to white men at similar CHD risk, fewer white women, black men and especially black women who were aware of their hyperlipidemia were treated and when treated, they were less likely to achieve control, even after adjusting for factors that influence health services utilization.


Author(s):  
Amy Murrell Taylor

This chapter focuses on the relationship between race and space—between competing ideas for how people of different races should reside spatially—by looking at the Union army’s various attempts to remove refugees en masse. These removals attempted to resettle the people in places far removed from active combat, including northern states, islands in the Mississippi River, and even Haiti. Some of these efforts bore a great deal of resemblance to antebellum colonization plans, and, as in those cases, black men and women in the Civil War largely resisted being sent away. Most of the removals were justified by white officials in environmental terms, driven by racial ideologies that linked particular climates and landscapes to people of color. The chapter also argues that removals were sometimes triggered by concerns about gender and sex too—by beliefs that the physical proximity of black women and white men in military encampments had made rape inevitable.


Author(s):  
Kristopher A. Teters

While many western Union officers came to support emancipation and even the enlistment of black troops, their racial attitudes changed very little. On the whole, officers continued to view black people as inferior, exotic, incapable, and even subhuman. Interactions with former slaves reinforced racial stereotypes. This intense prejudice was especially prominent in the Midwest where there were many discriminatory laws. Freeing the slaves, which many officers only supported as a practical necessity to win the war, was very different from seeing black people as anything close to equal with white people. But experiences with black men and women, particularly servants with whom Federals formed long-lasting personal bonds, often tempered racial prejudices on an individual level. Black men and women who assisted the Union army by providing information, resources, and aid in dangerous circumstances also won positive comments from officers. This softening of racial attitudes, however, almost never extended to the black population as a whole, and even ardent supporters of emancipation showed little sympathy for expanding black rights. The Civil War had eliminated slavery but had hardly solved the problem of racial prejudice.


2013 ◽  
Vol 304 (2) ◽  
pp. R164-R169 ◽  
Author(s):  
Lacy M. Alexander ◽  
Jessica L. Kutz ◽  
W. Larry Kenney

Localized exogenous R-tetrahydrobiopterin (R-BH4) corrects the deficit in local heat-induced vasodilation (VD) in hypercholesterolemic (HC) human skin through one of two plausible mechanisms: by serving as an essential cofactor to stabilizing endothelial nitric oxide (NO) synthase (eNOS) or through generalized antioxidant effects. We used the stereoisomer S-BH4, which has the same antioxidant properties but does not function as an essential NOS cofactor, to elucidate the mechanism by which R-BH4 restores cutaneous VD in HC humans. Intradermal microdialysis fibers were placed in 20 normocholesterolemic (NC), 13 midrange cholesterolemic (MC), and 18 HC (LDL: 94 ± 3, 124 ± 3 and 179 ± 6 mg/dl, respectively) men and women to perfuse Ringer (control site) and R-BH4. In 10 NC, 13 MC, and 9 HC subjects (LDL: 94 ± 3, 124 ± 3, 180 ± 10 mg/dl), S-BH4 was perfused at a third microdialysis site. Skin blood flow was measured during a standardized local heating protocol to elicit eNOS-dependent VD. After cutaneous vascular conductance (CVC = LDF/MAP) plateaued, NO-dependent VD was quantified by perfusing NG-nitro-l-arginine methyl ester (l-NAME). Data were normalized as %CVCmax. Fully expressed VD (NC: 97.9 ± 2.3 vs. MC: 85.4 ± 5.4, HC: 79.9 ± 4.2%CVCmax) and the NO-dependent portion (NC: 62.1 ± 3 vs. MC: 45.8 ± 3.9, HC: 35.7 ± 2.8%CVCmax) were reduced in HC (both P < 0.01 vs. NC), but only the fully expressed VD was reduced in MC ( P < 0.01 vs. NC). R-BH4 increased the fully expressed (93.9 ± 3.4%CVCmax; P < 0.01) and NO-dependent VD (52.1 ± 5.1%CVCmax; P < 0.01) in HC but not in NC or MC. S-BH4 increased full-expressed VD in HC ( P < 0.01) but did not affect NO-dependent VD in HC or MC. In contrast S-BH4 attenuated NO-dependent VD in NC (control: 62.1 ± 3 vs. S-BH4: 41.6 ± 7%CVCmax; P < 0.001). Exogenous R-BH4 restores NO-dependent VD in HC human skin predominantly through NOS coupling mechanisms but increases full expression of the local heating response through generalized antioxidant properties.


2002 ◽  
Vol 282 (1) ◽  
pp. H232-H236 ◽  
Author(s):  
Shubha Shastry ◽  
Michael J. Joyner

The binding of heat shock protein 90 (HSP90) to endothelial nitric oxide (NO) synthase (eNOS) can enhance eNOS activation. Studies have shown that the HSP90-specific inhibitor geldanamycin (GA) can cause attenuation of NO-mediated processes. Twenty subjects participated in one of two protocols. In each protocol, one forearm of each subject was instrumented with two intradermal microdialysis probes for drug delivery. Laser Doppler flowmeters were used to measure cutaneous blood flow. Skin sites were either treated with the endothelial agonist acetylcholine or locally heated to 42°C, a maneuver that evokes NO-mediated dilation. Interventions were performed with and without GA. In the presence of GA, maximal cutaneous vascular conductance (CVC) to ACh was 20 ± 3% lower than with ACh alone ( P < 0.001). During local heating, maximal CVC in the presence of GA was 22 ± 6% lower than during heating alone ( P < 0.01). The results show that GA can attenuate NO-mediated dilation in human skin, suggesting a potential role for HSP90 in activation of eNOS in the microcirculation.


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