title: Effects of Early Post-Ischemic Reperfusion and tPA on Cerebrovascular Function and Nitrosative Stress in Female Rats.
abstract: Stroke is a major health issue in women. Our previous studies in male rats showed decreased myogenic tone in middle cerebral arteries (MCAs) after ischemia and reperfusion (I/R), while tone in parenchymal arterioles (PAs) was increased. This vascular response may aggravate stroke damage in males by limiting reperfusion; however, the effect in females is not known. The current study investigated the effect of I/R and tissue plasminogen activator (tPA) on myogenic tone and reactivity of MCAs and PAs in female rats. Nitrosative stress by peroxynitrite and recruitment of inflammatory neutrophils to the microvasculature were also studied. Female rats were subjected to 2-h MCA filament occlusion (n = 16) or sham surgery (n = 17) and given tPA (1 mg/kg, i.v) or vehicle followed by 30-min reperfusion. Myogenic tone and reactivity were measured in isolated and pressurized MCAs and PAs from the same animals. Cerebrovascular F-actin, 3-nitrotyrosine (3-NT, peroxynitrite marker), and intravascular neutrophils were quantified. Myogenic tone and constriction to the nitric oxide synthase inhibitor Nω-nitro-L-arginine were decreased in MCAs but unchanged in PAs after I/R with no effect of tPA. F-actin and 3-NT expression were unaffected by I/R or tPA. Our study showed that MCAs from females, similar to what has been seen in males, are dilated after I/R and have decreased myogenic tone while tone in PAs was unchanged. Increased small vessel resistance may contribute to decreased reperfusion and worse outcome after stroke.
authors.affiliation: Department of Neurological Sciences, University of Vermont College of Medicine, HSRF 416A, 149 Beaumont Avenue, Burlington, VT, 05405, USA.
authors.forename: Hilda
authors.initials: H
authors.lastname: Ahnstedt
authors.affiliation: Department of Neurological Sciences, University of Vermont College of Medicine, HSRF 416A, 149 Beaumont Avenue, Burlington, VT, 05405, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Sweet
authors.affiliation: Department of Neurological Sciences, University of Vermont College of Medicine, HSRF 416A, 149 Beaumont Avenue, Burlington, VT, 05405, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Cruden
authors.affiliation: Department of Neurological Sciences, University of Vermont College of Medicine, HSRF 416A, 149 Beaumont Avenue, Burlington, VT, 05405, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Bishop
authors.affiliation: Department of Neurological Sciences, University of Vermont College of Medicine, HSRF 416A, 149 Beaumont Avenue, Burlington, VT, 05405, USA. marilyn.cipolla@med.uvm.edu.|Department of Obstetrics, Gynecology and Reproductive Sciences, University of Vermont College of Medicine, Burlington, VT, USA. marilyn.cipolla@med.uvm.edu.
authors.forename: Marilyn J
authors.initials: MJ
authors.lastname: Cipolla
mesh_terms: D000199:Actins / Q000378:metabolism; D000577:Amides / Q000627:therapeutic use; D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy*; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000378:metabolism; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D010052:Ovariectomy; D011725:Pyridines / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D015427:Reperfusion Injury / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D000199:Actins; D000577:Amides; D004791:Enzyme Inhibitors; D005343:Fibrinolytic Agents; D011725:Pyridines; C108830:Y 27632; C002744:3-nitrotyrosine; D014443:Tyrosine; D010959:Tissue Plasminogen Activator
keywords: 3-Nitrotyrosine; Cerebral ischemia; Middle cerebral arteries; Myogenic tone; Parenchymal arterioles; Reperfusion