Blunted Sensory Nerve‐Mediated Cutaneous Vasodilation in Black Women and the Relationship with Endothelin‐1 and L‐arginine

Abstract

In the U.S. the black population (BL) suffers from elevated prevalences of hypertension and cardiovascular disease relative to other racial groups. However, research specific to the mechanisms for these conditions in BL women (BW) remains remarkably devoid. Our laboratory has previously reported that BL individuals have a blunted sensory nerve-mediated cutaneous vasodilation during a standard local heating protocol relative to age and sex-matched white individuals. Furthermore, local blockade of NADPH oxidase and xanthine oxidase, using intradermal infusion of apocynin and allopurinol respectively, augmented this blunted response in BL men (BM) whereas there was no effect in BW. These data suggest divergent mechanisms mediating blunted sensory nerve-mediated cutaneous vasodilation in blacks. Two possible mechanistic pathways are heightened endothelin-1 (ET-1) activity and/or reduced L-arginine (L-ARG) bioavailability. Therefore, we tested the hypothesis that ET-1 overactivity and/or L-ARG insufficiency contribute to the blunted sensory-nerve-mdiated cutaneous vasodilation in BL women. Four intradermal microdialysis membranes were placed in the dorsal forearm of 7 BL women (mean±SD; age: 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. Sensory-nerve-mdiated cutaneous vasodilation was assessed as the CVC response averaged over a 60 s period of the initial dilation achieved at the onset of the local heating protocol. Site-specific maximal cutaneous blood flow was determined via combined sodium nitroprusside (28mM) infusion and 43°C heating. The CVC response during the initial dilation was calculated as a percent of site-specific maximum (%CVCmax). Sensory nerve-mediated vasodilation in BL women was 53 ± 15 %CVC­max at the Ringer's site (control). The was no effect on the response at the BQ-123 site (62 ± 20 %CVC­max), BQ-788 site (48 ± 11 %CVC­max), and the L-ARG site (49 ± 7 %CVC­max) relative to the Ringer's site (P > 0.05 for each comparison). Contrary to our hypothesis, these preliminary data suggest that the previously observed blunted sensory-nerve mediated vasodilation during local heating in BL women is not related to ET-1 overactivity and/or L-ARG insufficiency.