Cutaneous sensory nerve‐mediated microvascular vasodilation in normotensive and prehypertensive non‐Hispanic Blacks and Whites

Abstract

Relative to non-Hispanic Whites, non-Hispanic Blacks are disproportionately affected by elevated blood pressure (BP). It is unknown whether race or subclinical increases in BP affect the ability of cutaneous sensory nerves to induce cutaneous microvascular vasodilation. Sixteen participants who self-identified as non-Hispanic Black (n = 8) or non-Hispanic White (n = 8) were subgrouped as normotensive or prehypertensive. Participants were instrumented with three intradermal microdialysis fibers: (a) control, (b) 1 μM sodium nitroprusside (SNP), an exogenous nitric oxide (NO) donor, and (c) 20 mM N G -nitro-l-arginine methyl ester (L-NAME), a non-selective NO synthase inhibitor. A slow local heating protocol (33-40°C, 0.1°C/ min) was used to assess the onset of cutaneous sensory nerve-mediated vasodilation (temperature threshold) and skin blood flow was measured using laser-Doppler flowmetry. At control sites, the temperature threshold occurred at a higher temperature in non-Hispanic Blacks (normotensive: 37.2 ± 0.6°C, prehypertensive: 38.9 ± 0.5°C) compared to non-Hispanic Whites (normotensive: 35.2 ± 0.8°C, prehypertensive:35.2 ± 0.9°C). L-NAME shifted the temperature threshold higher in non-Hispanic Whites (normotensive: 37.8 ± 0.7°C, prehypertensive: 38.2 ± 0.8°C), but there was no observed effect in non-Hispanic Blacks. SNP did not affect temperature threshold in non-Hispanic Whites, but shifted the temperature threshold lower in non-Hispanic Blacks (normotensive: 34.6 ± 1.2°C, prehypertensive: 34.8 ± 1.1°C). SNP mitigated differences in temperature threshold across all groups. There was no effect found for BP status in either the non-Hispanic Black or non-Hispanic White groups. These data suggest that reduced NO bioavailability affects the ability of cutaneous sensory nerves to induce microvascular vasodilation in young, otherwise healthy non-Hispanic Blacks. K E Y W O R D S human, nitric oxide, skin How to cite this article: Turner CG, Miller JT, Otis JS, Hayat MJ, Quyyumi AA, Wong BJ. Cutaneous sensory nerve-mediated microvascular vasodilation in normotensive and prehypertensive non-Hispanic Blacks and Whites. Physiol Rep. 2020;8:e14437.

Sensory nerve-mediated and nitric oxide-dependent cutaneous vasodilation in normotensive and prehypertensive non-Hispanic blacks and whites

“…Type 2 diabetes and chemotherapy are widely known to be risk factors for developing sensory nerve dysfunction (i.e., diabetic sensory neuropathy and chemotherapy-induced neuropathy, respectively), but some evidence suggests race and blood pressure may also be risk factors for developing sensory nerve dysfunction (11,17,21,51). Additionally, we recently observed that the temperature threshold for cutaneous sensory nerve activation is shifted to a higher temperature in non-Hispanic blacks; however, we were unable to assess the magnitude of sensory nerve-mediated vasodilation in our previous study (52). A recent study by Patik et al (45) found that the magnitude of the initial peak response was reduced in non-Hispanic blacks relative to non-Hispanic whites; however, determination of the contribution of sensory nerves to the initial peak was not assessed in that particular study.…”

“…Whether race and/or blood pressure status adversely affect sen-sory nerve function is not completely known; however, some evidence suggests overt hypertension and race may be risk factors for the development of sensory neuropathy (11,17,21). Our laboratory recently demonstrated that the temperature threshold eliciting cutaneous sensory nerve activation is shifted to a higher temperature in non-Hispanic blacks relative to non-Hispanic whites, and this rightward shift is largely due to a reduction in bioavailable NO (52). In this previous study we used a slow, ramp local heating protocol and were unable to determine the magnitude of sensory nerve-mediated vasodilation (27,52).…”

“…Our laboratory recently demonstrated that the temperature threshold eliciting cutaneous sensory nerve activation is shifted to a higher temperature in non-Hispanic blacks relative to non-Hispanic whites, and this rightward shift is largely due to a reduction in bioavailable NO (52). In this previous study we used a slow, ramp local heating protocol and were unable to determine the magnitude of sensory nerve-mediated vasodilation (27,52). Although microvascular NO-dependent vasodilation is reduced in hypertension (5,12,15,16,20,37,49) and healthy young non-Hispanic blacks (30,35,36,45), it remains unknown whether subclinical elevations in blood pressure (i.e., prehypertension) affect NOdependent vasodilation in either non-Hispanic whites or non-Hispanic blacks.…”

Women with a history of preeclampsia have preserved sensory nerve‐mediated dilatation in the cutaneous microvasculature

“…The pathophysiology of sensory neuropathy is linked to microvascular and endothelial dysfunction (Cameron et al., 2001) and we originally hypothesized that this dilatation would be attenuated in our patient group. Indeed, prehypertensive adults and non‐hypertensive black men and women have an attenuated cutaneous sensory nerve‐mediated vasodilatation response, reflective of and accompanied by reductions in endothelium‐dependent NO‐mediated dilatation (Patik et al., 2018; Turner et al., 2020; Wong et al., 2020). In these studies, as with ours, local heating applied to the skin was used to activate the sensory nerve‐mediated increase in skin blood flow.…”

“…The pathophysiology of sensory neuropathy is linked to microvascular and endothelial dysfunction (Cameron et al., 2001) and sensory nerve dysfunction exacerbates vascular dysfunction in rodent models of hypertension (Watson et al., 2002). Indeed, overt hypertension may be an independent risk factor for sensory neuropathy in humans (Cohen et al., 1998; Hebert et al., 2017), and prehypertensive adults have an attenuated cutaneous sensory nerve‐mediated vasodilatation response, reflective of and accompanied by reductions in endothelium‐dependent NO‐mediated dilatation (Turner et al., 2020; Wong et al., 2020). Together, these data suggest that sensory nerve‐mediated microvascular dilatation may be attenuated in populations with attenuated NO bioavailability, and that this attenuation may contribute to the development of CVD.…”