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

Abstract

New findings: What is the central question of this study? Are sensory nerve-mediated vasodilatation and the NO-dependent contribution to that response attenuated in the cutaneous microvasculature of women who have had preeclampsia? What is the main finding and its importance? Women who have had preeclampsia demonstrate attenuated microvascular endothelium-dependent dilatation compared to women with a history of uncomplicated pregnancy. However, there are no differences in sensory nerve-mediated vasodilatation between groups. This suggests that the neurogenic response is not altered following preeclampsia, and that the NO-dependent vasodilatation of the neurogenic response is not related to endothelium-dependent NO-mediated dilatation in these women.

Abstract: Women who have had preeclampsia (PE) demonstrate microvascular endothelial dysfunction, mediated in part by reduced nitric oxide (NO)-dependent mechanisms. Localized heating of the skin induces a biphasic vasodilatation response: a sensory nerve-mediated initial peak, followed by a sustained endothelium-dependent plateau. We have previously shown that the endothelium-dependent plateau is attenuated in PE. However, it is unknown if the sensory nerve-mediated initial peak is similarly attenuated. Therefore, the purpose of this study was to examine the effect of PE history on sensory nerve-mediated vasodilatation and the NO-dependent contribution to that response. We hypothesized that PE would have an attenuated initial peak and a reduced NO-dependent contribution to that response compared to women with a history of normotensive pregnancy (healthy controls, HC). Nine HC (31 ± 4 years) and nine PE (28 ± 6 years) underwent a standard local heating protocol (42°C; 0.1°C s^-1 ). Two intradermal microdialysis fibres were placed in the skin of the ventral forearm for the continuous local delivery of lactated Ringer solution alone (control) or 15-mM N^G -nitro-l-arginine methyl ester for nitric oxide synthase (NOS) inhibition. Red blood cell flux was measured at each site by laser Doppler flowmetry (LDF). Cutaneous vascular conductance was calculated (CVC = LDF/mean arterial pressure) and normalized to maximum (%CVC_max ; 28-mM SNP + local heat 43°C). There were no differences in the initial peak between groups (HC: 79 ± 8 vs. PE: 80 ± 10%CVC_max ; P = 0.936). NOS inhibition attenuated the initial peak in both HC (57 ± 18% CVC_max ; P = 0.003) and PE (54 ± 10%CVC_max ; P = 0.002). However, there were no differences in the NO-dependent portion of the initial peak (HC: 23 ± 16 vs. PE: 24 ± 9%; P = 0.777). The local heating plateau (HC: 99 ± 4 vs. PE: 88 ± 7%CVC_max ; P = 0.001) and NO contribution to the plateau (HC: 31 ± 9 vs. PE: 17 ± 14%; P = 0.02) were attenuated in PE. There was no relation between NO-dependent dilatation in the initial peak and NO-dependent dilatation in the plateau across groups (R² = 0.005; P = 0.943). Women who have had PE demonstrate attenuated microvascular endothelium-dependent dilatation. However, there are no differences in sensory nerve-mediated vasodilatation following PE, suggesting that the NO-dependent vasodilatation of the neurogenic response is not related to endothelium-dependent NO-mediated dilatation in these women.

Keywords: microvascular; nitric oxide; preeclampsia; sensory nerve.