title: Age and sex differences in vascular responsiveness in healthy and trauma patients: contribution of estrogen receptor-mediated Rho kinase and PKC pathways.
abstract: Several medical conditions exhibit age- and sex-based differences. Whether or not traumatic shock exhibits such differences with regard to vascular responsiveness is not clear. In a cohort of 177 healthy subjects and 842 trauma patients (21-82 years) as well as different ages (4, 8, 10, 14, 18, and 24 wk; 1 and 1.5 years) and sexes of Sprague-Dawley normal and traumatic shock rats, the age- and sex-based differences of vascular responsiveness and the underlying mechanisms were investigated. Middle-aged and young women as well as female rats of reproductive age had higher vascular responsiveness in the normal condition and a lower decrease in vascular responsiveness after traumatic shock than older men and male rats of identical age. Exogenous supplementation of 17β-estrdiol increased vascular reactivity in both male and femal rats of 8-24 wk and preserved vascular responsiveness in rats following traumatic shock. No effect was observed in rats 1 to 1.5 years. These protective effects of estrogen were closely related to G protein-coupled receptor (GPR)30, estrogen receptor-mediated Rho kinase, and PKC pathway activation. Vascular responsiveness exhibits age- and sex-based differences in healthy subjects and trauma patients. Estrogen and its receptor (GPR30) mediated activation of Rho kinase and PKC using genomic and nongenomic mechanisms to elicit protective effects in vascular responsiveness. This finding is important for the personalized treatment for several age- and sex-related diseases involving estrogen.
authors: State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China;
authors: Tao
authors: T
authors: Li
authors: Xudong
authors: X
authors: Xiao
authors: Jie
authors: J
authors: Zhang
authors: Yu
authors: Y
authors: Zhu
authors: Yi
authors: Y
authors: Hu
authors: Jiatao
authors: J
authors: Zang
authors: Kaizhi
authors: K
authors: Lu
authors: Tiande
authors: T
authors: Yang
authors: Hengjiang
authors: H
authors: Ge
authors: Xiaoyong
authors: X
authors: Peng
authors: Dan
authors: D
authors: Lan
authors: Liangming
authors: L
authors: Liu
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004958:Estradiol / Q000008:administration & dosage; D004967:Estrogens / Q000502:physiology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D012737:Sex Factors; D012771:Shock, Hemorrhagic / Q000503:physiopathology; D014947:Wounds and Injuries / Q000503:physiopathology*; D054460:rho-Associated Kinases / Q000502:physiology*
chemical_list: D004967:Estrogens; C109584:GPER1 protein, human; C520305:Gper1 protein, rat; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D004958:Estradiol; D054460:rho-Associated Kinases; D011493:Protein Kinase C
keywords: PKC; Rho kinase; age; estrogen; estrogen receptor; sex; vascular reactivity