Blunted Cutaneous Thermal Reactivity in Black Women and the Relationship with Endothelin‐1 and L‐arginine

Abstract

The black population (BL) has elevated rates of hypertension and cardiovascular disease relative to other populations. However, research specific to the mechanisms for these conditions in BL women (BW) remains remarkably devoid. Our group recently demonstrated impaired microvascular function in young, BL men (BM) and BW. Further, inhibition of oxidative stress from xanthine and NADPH oxidases restored microvascular function in BM, while no such effect was observed in BW suggesting divergent mechanisms of microvascular dysfunction between these populations. Two possible candidate mechanisms are heightened endothelin‐1 (ET‐1) activity and/or reduced L‐arginine (L‐ARG) bioavailability, both of which have been noted in BW, but not specifically linked to microvascular dysfunction. Therefore, this study tested the hypothesis that ET‐1 overactivity and/or L‐ARG insufficiency contribute to the blunted microvascular function observed in young, BW. To test this hypothesis, four intradermal microdialysis membranes were placed in the dorsal forearm of 4 white women (WW) and 6 BW (mean±SD; age: 22 ± 2 vs. 21 ± 3) and the cutaneous vascular conductance (CVC: cutaneous blood flow/mean arterial pressure) response to a standard local heating protocol was assessed. Following trauma resolution, each site received one of four, 30‐min infusions: lactated Ringer’s (control), BQ‐123 (500nM; ET receptor type A antagonist), BQ‐788 (300nM; ET receptor type B antagonist), or L‐ARG (10mM). After a 10‐min baseline at 33°C, skin temperature was elevated to 39°C for ~30‐min to assess local cutaneous thermal reactivity. L‐NAME (20mM) was then infused at all sites to inhibit nitric oxide (NO) synthase and quantify the NO contribution to the CVC response. Site‐specific maximal cutaneous blood flow was then determined via combined sodium nitroprusside (28mM) infusion and 43°C heating. The CVC response during each stage was calculated as a percent of site‐specific maximum (%CVCmax) while the NO contribution was calculated as a delta between the 39°C plateau and the L‐NAME nadir (Δ%CVCmax). During local heating, BW exhibited blunted CVC responses compared to WW (control: 35.3 ± 28.7 vs. 50.6 ± 8.1 %CVC‐max; BQ‐123: 41.6 ± 12.0 vs. 64.5 ± 9.2 %CVCmax; BQ‐788: 25.9 ± 18.9 vs. 59.5 ± 13.9 %CVCmax; L‐ARG: 29.6 ± 12.1 vs. 54.6 ± 11.9 %CVCmax; respectively; main effect: P = 0.03). BW also exhibited a reduced NO contribution to vasodilation relative to WW (control: 19.4 ± 8.6 vs. 37.6 ± 7.4 Δ%CVCmax; BQ‐123: 30.8 ± 11.8 vs. 47.8 ± 7.6 Δ%CVCmax; BQ‐788: 17.3 ± 14.7 vs. 44.0 ± 14.2 Δ%CVCmax; L‐ARG: 21.5 ± 9.2 vs. 40.0 ± 12.3 Δ%CVCmax; respectively; main effect: P < 0.01). No interactions were noted for either race‐by‐drug comparison (P > 0.05). These preliminary data suggest that BW exhibit blunted NO‐mediated vasodilation to local heating compared to WW. However, individual ET‐1 receptor activity and reduced L‐ARG bioavailability do not appear to influence the blunted dilatory response.Support or Funding InformationResearch Support: ACSM, Texas ACSM, and The University of Texas at Arlington CONHI (JDA)