Contributions of Endothelin-1 and L-arginine to Blunted Cutaneous Microvascular Function in Young, Black Women

2021 ◽  
Author(s):  
John D. Akins ◽  
Rauchelle E. Richey ◽  
Jeremiah C. Campbell ◽  
Zachary T. Martin ◽  
Guillermo Olvera ◽  
...  
Keyword(s):  
Black Women ◽  
Vascular Function ◽  
Local Heating ◽  
Type A ◽  
Microvascular Function ◽  
Receptor Type ◽  
Endothelin 1 ◽  
Young Black Women ◽  
Racial Ethnic ◽  
Cutaneous Vascular Conductance

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.

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 ◽  
...  
Keyword(s):  
Sex Differences ◽  
Black Women ◽  
Black Men ◽  
Local Heating ◽  
Black Population ◽  
Control Site ◽  
Microvascular Function ◽  
Vascular Conductance ◽  
Men And Women ◽  
Cutaneous Vascular Conductance

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.

Abstract P276: A High Sodium Diet Reduces Cutaneous Microvascular Function In Normotensive Individuals With Salt Sensitive Blood Pressure

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Jordan C Patik ◽  
Joseph M Stock ◽  
Nathan T Romberger ◽  
Shannon L Lennon ◽  
William B Farquhar ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vascular Function ◽  
Sodium Intake ◽  
Local Heating ◽  
Urinary Sodium Excretion ◽  
Microvascular Function ◽  
Dietary Sodium ◽  
Heating Unit ◽  
Doppler Flowmetry ◽  
High Sodium

Impaired vascular function likely contributes to the association between dietary sodium intake and the development of cardiovascular disease. Using the cutaneous microvasculature as a model, we have previously shown that a high sodium (HS) diet blunts local heating-induced vasodilation in normotensive individuals with salt resistant (SR) blood pressure (BP). However, the effect of a HS diet on the cutaneous microvasculature in normotensive salt sensitive (SS) individuals remains unclear. Therefore, we tested the hypothesis that cutaneous microvascular function is reduced by a HS diet to a greater degree in SS compared to SR individuals. After each 7-day controlled feeding diet (low sodium (LS) = 20 mmol/day; HS = 300 mmol/day), an intradermal microdialysis fiber was inserted in the ventral forearm and perfused with Ringer’s solution. Skin blood flow (SkBF) was continuously monitored via laser Doppler flowmetry and a local heating unit was placed over the fiber and heated to 42°C until SkBF reached a stable plateau. Site-specific maximal SkBF was determined by perfusing 28mM sodium nitroprusside and heating to 43°C. Mean arterial pressure (MAP) was assessed at regular intervals on the contralateral arm and was used to calculate cutaneous vascular conductance (CVC = SkBF / MAP). Subjects wore a 24-hr ambulatory BP monitor and collected their urine on the final day of each diet. Fourteen subjects (9W / 5M, 42 ± 14 yr) whose MAP increased >5 mmHg (Δ8 ± 1 mmHg) on the HS diet were defined as SS and were compared to 14 age- (43± 14 yr) and sex-matched SR subjects (Δ1 ± 3 mmHg). SS and SR had similar MAP at baseline (88 ± 9 vs. 90 ± 8 mmHg, P = 0.88) and urinary sodium excretion was increased similarly across groups by the HS diet (Δ239 ± 104 vs. Δ220 ± 66 mmol / 24 hr, P = 0.20). Cutaneous vasodilation in response to local heating was decreased on the HS diet relative to the LS diet in both SS (Δ-9 ± 9 %CVCmax, P = 0.005) and SR (Δ-9 ± 9 %CVCmax, P=0.005); however, there was not a group x diet interaction (P = 0.99). In contrast to our hypothesis, these results suggest that the deleterious effects of high sodium diets on cutaneous microvascular function are similar in normotensive salt sensitive and salt resistant individuals.

scholarly journals New approach to measure cutaneous microvascular function: an improved test of NO-mediated vasodilation by thermal hyperemia

2014 ◽  
Vol 117 (3) ◽  
pp. 277-283 ◽  
Author(s):  
Patricia J. Choi ◽  
Vienna E. Brunt ◽  
Naoto Fujii ◽  
Christopher T. Minson
Keyword(s):  
Healthy Subjects ◽  
Rapid Heating ◽  
Local Heating ◽  
Ringer Solution ◽  
No Synthase ◽  
Microvascular Function ◽  
Vascular Conductance ◽  
New Approach ◽  
Cutaneous Vascular Conductance

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.

Evidence of Reduced Peripheral Microvascular Function in Young Black Women Across the Menstrual Cycle

2021 ◽  
Author(s):  
Michele N. D'Agata ◽  
Elissa K. Hoopes ◽  
Felicia R. Berube ◽  
Alexandra E. Hirt ◽  
Andrew V. Kuczmarski ◽  
...  
Keyword(s):  
Blood Flow ◽  
Black Women ◽  
Menstrual Cycle ◽  
Racial Disparity ◽  
Vascular Function ◽  
White Women ◽  
Microvascular Function ◽  
Hormonal Contraceptives ◽  
Flow Area ◽  
Leg Blood Flow

Black women (BLW) have a higher prevalence of cardiovascular disease (CVD) morbidity and mortality compared to white women (WHW). A racial disparity in CVD risk has been identified early in life as young adult BLW demonstrate attenuated vascular function compared to WHW. Previous studies comparing vascular function between premenopausal WHW and BLW have been limited to the early follicular (EF) phase of the menstrual cycle, which may not reflect their vascular function during other menstrual phases. Therefore, we evaluated peripheral microvascular function in premenopausal WHW and BLW using passive leg movement (PLM) during three menstrual phases: EF, ovulation (OV), and mid-luteal (ML). We hypothesized that microvascular function would be augmented during the OV and ML phases compared to the EF phase in both groups, but would be attenuated in BLW compared to WHW at all three phases. PLM was performed on 26 apparently healthy premenopausal women not using hormonal contraceptives: 15 WHW (23±3 years), 11 BLW (24±5 years). There was a main effect of race on the overall change in leg blood flow (∆LBF) (p=0.01) and leg blood flow area under the curve (LBF AUC) (p=0.02), such that LBF was lower in BLW. However, there was no effect of phase on ∆LBF (p=0.69) or LBF AUC (p=0.65), nor an interaction between race and phase on ∆LBF (p=0.37) or LBF AUC (p=0.75). Despite peripheral microvascular function being unchanged across the menstrual cycle, a racial disparity was apparent as microvascular function was attenuated in BLW compared to WHW across the menstrual cycle.

scholarly journals Risk Factors in Normal-Tension Glaucoma and High-Tension Glaucoma in relation to Polymorphisms of Endothelin-1 Gene and Endothelin-1 Receptor Type A Gene

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Dominika Wróbel-Dudzińska ◽  
Ewa Kosior-Jarecka ◽  
Urszula Łukasik ◽  
Janusz Kocki ◽  
Agnieszka Witczak ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Intraocular Pressure ◽  
Clinical Condition ◽  
Type A ◽  
Normal Tension Glaucoma ◽  
Receptor Type ◽  
Endothelin 1 ◽  
Arterial Blood ◽  
High Tension

The aimof the research is to analyse the influence of polymorphisms of endothelin-1 gene and endothelin-1 receptor type A gene on the clinical condition of patients with primary open angle glaucoma.Methods. 285 Polish patients took part in the research (160 normal-tension glaucoma and 125 high-tension glaucoma). DNA was isolated by standard methods and genotype distributions of four polymorphisms in genes encoding endothelin-1 (K198N) and endothelin-1 receptor type A polymorphisms (C1222T, C70G, and G231A) were determined. Genotype distributions were compared between NTG and HTG groups. The clinical condition of participants was examined for association with polymorphisms.Results. A similar frequency of occurrence of the polymorphic varieties of the studied genes was observed in patients with NTG and HTG. There is no relation between NTG risk factors and examined polymorphisms. NTG patients with TT genotype of K198N polymorphism presented with the lowest intraocular pressure in comparison to GG + GT genotype (p=0.03). In NTG patients with CC genotype of C1222T polymorphism (p=0.028) and GG of C70G polymorphism (p=0.03) the lowest values of mean blood pressure were observed.Conclusions. The studied polymorphic varieties (K198N, C1222T) do have an influence on intraocular pressure as well as arterial blood pressure in NTG patients.

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