title: Myoendothelial gap junction frequency does not account for sex differences in EDHF responses in rat MCA.
abstract: Previous findings from our laboratory have shown that dilations to endothelium-derived hyperpolarizing factor (EDHF) in rat middle cerebral artery (MCA) are less in females compared to males. Myoendothelial gap junctions (MEGJs) appear to mediate the transfer of hyperpolarization between endothelium and smooth muscle in males. In the present study, we hypothesized that MEGJs are the site along the EDHF pathway which is compromised in female rat MCA. Membrane potential in endothelium was measured using the voltage-sensitive dye di-8-ANEPPS and in smooth muscle using intracellular glass microelectrodes in the presence of l-NAME (3x10(-5 )M) and indomethacin (10(-5 )M). Electron microscopy was used to assess MEGJ characteristics. In endothelial cells, the di-8-ANEPPS fluorescence ratio change to 10(-5 )M UTP was similar in males (-2.9+/-0.5%) and females (-3.2+/-0.2%), indicating comparable degrees of endothelial cell hyperpolarization. However, smooth muscle cell hyperpolarization to 10(-5 )M UTP was significantly attenuated in females (0 mV hyperpolarization; -31+/-1.5 mV resting) compared to males (8 mV hyperpolarization; -28+/-1.7 mV resting). Ultrastructural evidence suggested that MEGJ frequency and area of contact were comparable between males and females. Taken together, our data suggest that in rat MCA, MEGJ frequency does not account for the reduced EDHF responses observed in females compared to males. We conclude that reduced myoendothelial coupling and/or homocellular coupling within the media may account for these differences.
authors.affiliation: Department of Anesthesiology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. egolding@bcm.tmc.edu
authors.forename: Elke M
authors.initials: EM
authors.lastname: Sokoya
authors.forename: Alan R
authors.initials: AR
authors.lastname: Burns
authors.forename: Sean P
authors.initials: SP
authors.lastname: Marrelli
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D001685:Biological Factors / Q000378:metabolism*; D004338:Drug Combinations; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D012737:Sex Factors
chemical_list: C089669:1-(3-sulfonatopropyl)-4-(beta-(2-(di-n-octylamino)-6-naphthyl)vinyl)pyridinium betaine; D001685:Biological Factors; D004338:Drug Combinations; D011726:Pyridinium Compounds; C067410:endothelium-dependent hyperpolarization factor; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin