RESUMO
The endothelin-B (ETB) receptor is a key regulator of vascular endothelial function in women. We have previously shown that the ETB receptor mediates vasodilation in young women, an effect that is lost after menopause. However, the direct impact of changes in estradiol (E2) on ETB receptor function in women remains unclear. Therefore, the purpose of this study was to test the hypothesis that E2 exposure modulates ETB receptor-mediated dilation in young women. Fifteen young women (24 ± 4 yr, 24 ± 3 kg/m2) completed the study. Endogenous sex hormone production was suppressed with daily administration of a gonadotropin-releasing hormone antagonist (GnRHant; Ganirelix) for 10 days; E2 (0.1 mg/day, Vivelle-Dot patch) was added back on days 4-10. We measured vasodilation in the cutaneous microcirculation (microvascular endothelial function) via local heating (42°C) on day 4 (GnRHant) and day 10 (GnRHant + E2) using laser Doppler flowmetry coupled with intradermal microdialysis during perfusions of lactated Ringer's (control) and ETB receptor antagonist (BQ-788, 300 nM). During GnRHant, vasodilatory responses to local heating were enhanced with ETB receptor blockade (control: 83 ± 9 vs. BQ-788: 90 ± 5%CVCmax, P = 0.004). E2 administration improved vasodilation in the control site (GnRHant: 83 ± 9 vs. GnRHant + E2: 89 ± 8%CVCmax, P = 0.036). Furthermore, cutaneous vasodilatory responses during ETB receptor blockade were blunted after E2 administration (control: 89 ± 8 vs. BQ-788: 84 ± 8%CVCmax, P = 0.047). These data demonstrate that ovarian hormones, specifically E2, modulate ETB receptor function and contribute to the regulation of microvascular endothelial function in young women.NEW & NOTEWORTHY The endothelin-B (ETB) receptor mediates vasodilation in young women, an effect lost following menopause. It is unclear whether these alterations are due to aging or changes in estradiol (E2). During endogenous hormone suppression (GnRH antagonist), blockade of ETB receptors enhanced cutaneous microvascular vasodilation. However, during E2 administration, blockade of ETB receptors attenuated vasodilation, indicating that the ETB receptor mediates dilation in the presence of E2. In young women, ETB receptors mediate vasodilation in the presence of E2, an effect that is lost when E2 is suppressed.
Assuntos
Antagonistas do Receptor de Endotelina B/farmacologia , Estradiol/farmacologia , Estrogênios/farmacologia , Receptor de Endotelina B/metabolismo , Vasodilatação , Adulto , Feminino , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/farmacologia , Antagonistas de Hormônios/farmacologia , Humanos , Microvasos/efeitos dos fármacos , Microvasos/metabolismo , Microvasos/fisiologia , Oligopeptídeos/farmacologia , Piperidinas/farmacologia , Pele/irrigação sanguíneaRESUMO
OBJECTIVE: The rate of areal bone mineral density (aBMD) loss at the knee (distal femur (DF) and proximal tibia ) and hip (femoral neck (FN) and total hip (TH)) was determined in persons with traumatic spinal cord injury (SCI) who were stratified into subgroups based on time since injury (TSI). DESIGN: Cross-sectional retrospective review. SETTING: Department of Veterans Affairs Medical Center and Private Rehabilitation Hospital. PARTICIPANTS: Data on 105 individuals with SCI (TSI ≤12 months, nâ¯=â¯19; TSI 1-5 years, nâ¯=â¯35; 6-10 years, nâ¯=â¯19; TSI 11-20 years, nâ¯=â¯16; TSI >20 years, nâ¯=â¯15) and 17 able-bodied reference (ABref) controls. INTERVENTIONS: NA Main Outcome Measures: The knee and hip aBMD values were obtained by dual energy X-ray absorptiometry (GE Lunar iDXA) using standard clinical software for the proximal femur employed in conjunction with proprietary research orthopedic knee software applications. Young-normal (T-score) and age-matched (Z-scores) standardized scores for the FN and TH were obtained using the combined GE Lunar/National Health and Nutrition Examination Survey (NHANES III) combined reference database. RESULTS: When groups were stratified and compared as epochs of TSI, significantly lower mean aBMD and reference scores were observed as TSI increased, despite similar mean ages of participants among the majority of TSI epoch subgroups. Loss in aBMD occurred at the distal femur (DF), proximal tibia (PT), FN, and TH with 46%, 49%, 32%, and 43% of the variance in loss, respectively, described by the exponential decay curves with a time to steady state (tss) occurring at 14.6, 11.3, 14, and 6.2 years, respectively, after SCI. CONCLUSIONS: Sublesional bone loss after SCI was marked and occurred as an inverse function of TSI. For aBMD at the hip and knee, tss extended into the second decade after SCI.