Women with a History of Preeclampsia Have Preserved Neurogenically‐Mediated Dilation in the Cutaneous Microvasculature

Abstract

Women who have had preeclampsia (PrEC) demonstrate microvascular endothelial dysfunction, mediated in part by reduced nitric oxide (NO)-dependent mechanisms. Localized heating of the skin induces a biphasic vasodilation response: a neurogenically-mediated initial peak, followed by a sustained endothelium-dependent plateau. We have previously shown that the endothelium-dependent plateau is attenuated in PrEC, due to attenuated NO-dependent dilation. However, it is unknown if the same is true concerning the neurogenically-mediated initial peak. The purpose of this study was to (1) examine the effect of preeclampsia history on neurogenically-mediated vasodilation and the NO-dependent contribution to that response, and (2) examine the relation between NO-dependent neurogenic dilation and the NO-dependent portion of the endothelium-dependent plateau. We hypothesized that PrEC would have an attenuated initial peak response and a reduced NO-dependent contribution to that response compared to women with a history of normotensive pregnancy (HC). Six HC (31±2yrs, 7±2 months post-partum) and 7 PrEC (29±2yrs, 7±3months post-partum) underwent a standard local heating protocol (42°C; 0.1°C·s-1). Two intradermal microdialysis fibers were placed in the skin of the ventral forearm for the continuous local delivery of Lactated Ringer's alone (control) or 15mM NG-nitro-L-arginine methyl ester (L-NAME) for nitric oxide synthase (NOS)-inhibition. Red blood cell flux was measured at each site via laser-Doppler flowmetry (LDF). Cutaneous vascular conductance was calculated (CVC=LDF/mean arterial pressure) and normalized to maximum (%CVCmax; 28mM SNP + local heat 43°C). NO-dependent dilation was calculated within-subject as the difference between control and NOS-inhibited sites. There were no differences in the initial peak between groups (HC: 80±5 vs PrEC: 79±5 %CVCmax; p=.88). NOS-inhibition attenuated the initial peak in both HC (Control: 80±5 vs L-NAME: 57±9 %CVCmax; p=0.02) and PrEC (Control: 79±5 vs L-NAME: 53±6 %CVCmax; p=0.004). However, there were no group differences in the NO-dependent portion of initial peak (HC: 23±8 vs PrEC: 24±5 %CVCmax; p=0.97). The local heating plateau (HC: 99±2 vs PrEC: 85±1 %CVCmax; p<0.001) and NO-contribution to the plateau (HC: 47±5 vs PrEC: 14±5 %CVCmax; p<0.001) were attenuated in PrEC compared to HC. There was no relation between NO-dependent dilation in the initial peak and NO-dependent dilation in the plateau across groups (R2 = 0.05; p = 0.51). Women who have had preeclampsia demonstrate attenuated microvascular endothelium-dependent dilation compared to women with a history of uncomplicated pregnancy. However, there are no differences in neurogenically-mediated vasodilation between the groups, suggesting that the NO-dependent vasodilation of the neurogenic response is not related to endothelium-dependent NO-mediated dilation in these women.