Original ArticleOvariectomy Reduces Vasocontractile Responses of Rat Middle Cerebral Arteries After Focal Cerebral IschemiaRehnström, Mimmi MD, MSc*; Ahnstedt, Hilda PhD*; Krause, Diana N. PhD†; Edvinsson, Marie Louise PhD‡; Haanes, Kristian Agmund PhD§; Edvinsson, Lars MD, PhD*,§Author Information *Department of Experimental Vasc Res, Clinical Sciences, Lund University, Sweden; †Department of Pharmacology, School of Medicine, University of California at Irvine, Irvine, CA; ‡Department of Emergency and Internal Medicine, Skåne University Hospital, Sweden; and §Department of Clinical and Experimental Research, Rigshospitalet Glostrup, Denmark. Correspondence: Lars Edvinsson, MD, PhD, Department of Experimental Vasc Res, Clinical Sciences, Lund University, Sölvegatan 17 BMC A13, SE-221 84 Lund, Sweden (e-mail: [email protected]). Supported by the Swedish Heart Lung Foundation [no. 20130271] and the KA Wallenberg foundation [no. KAW 2016.0081]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors report no conflicts of interest. Journal of Cardiovascular Pharmacology: January 2022 - Volume 79 - Issue 1 - p e122-e128 doi: 10.1097/FJC.0000000000001158 Buy Metrics Abstract Effects of sex hormones on stroke outcome are not fully understood. A deleterious consequence of cerebral ischemia is upregulation of vasoconstrictor receptors in cerebral arteries that exacerbate stroke injury. Here, we tested the hypothesis that female sex hormones alter vasocontractile responses after experimental stroke in vivo or after organ culture in vitro, a model of vasocontractile receptor upregulation. Female rats with intact ovaries and ovariectomized (OVX) females treated with 17β-estradiol, progesterone, or placebo were subjected to transient, unilateral middle cerebral artery occlusion followed by reperfusion (I/R). The maximum contractile response, measured my wire myography, in response to the endothelin B receptor agonist sarafotoxin 6c was increased in female arteries after I/R, but the maximum response was significantly lower in arteries from OVX females. Maximum contraction mediated by the serotonin agonist 5-carboxamidotryptamine was diminished after I/R, with arteries from OVX females showing a greater decrease in maximum contractile response. Contraction elicited by angiotensin II was similar in all arteries. Neither estrogen nor progesterone treatment of OVX females affected I/R-induced changes in endothelin B– and 5-carboxamidotryptamine–induced vasocontraction. These findings suggest that sex hormones do not directly influence vasocontractile alterations that occur after ischemic stroke; however, loss of ovarian function does impact this process. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.