caa a22 4500 606233679 CHVBK 20210128101233.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s11010-015-2368-4 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2368-4 High salt diet modulates vascular response in A2AAR+/+ and A2AAR−/− mice: role of sEH, PPARγ, and KATP channels [Elektronische Daten] [Isha Pradhan, Catherine Ledent, S. Mustafa, Christophe Morisseau, Mohammed Nayeem] This study aims to investigate the signaling mechanism involved in HS-induced modulation of adenosine-mediated vascular tone in the presence or absence of adenosine A2A receptor (A2AAR). We hypothesized that HS-induced enhanced vascular relaxation through A2AAR and epoxyeicosatrienoic acid (EETs) is dependent on peroxisome proliferator-activated receptor gamma (PPARγ) and ATP-sensitive potassium channels (KATP channels) in A2AAR+/+ mice, while HS-induced vascular contraction to adenosine is dependent on soluble epoxide hydrolase (sEH) that degrades EETs in A2AAR−/− mice. Organ bath and Western blot techniques were conducted in HS (4% NaCl) and normal salt (NS, 0.45% NaCl)-fed A2AAR+/+ and A2AAR−/− mouse aorta. We found that enhanced vasodilation to A2AAR agonist, CGS 21680, in HS-fed A2AAR+/+ mice was blocked by PPARγ antagonist (T0070907) and KATP channel blocker (Glibenclamide). Also, sEH inhibitor (AUDA)-dependent vascular relaxation was mitigated by PPARγ antagonist. PPARγ agonist (Rosiglitazone)-induced relaxation in HS-A2AAR+/+ mice was attenuated by KATP channel blocker. Conversely, HS-induced contraction in A2AAR−/− mice was attenuated by sEH inhibitor. Overall, findings from this study that implicates the contribution of EETs, PPARγ and KATP channels downstream of A2AAR to mediate enhanced vascular relaxation in response to HS diet while, role of sEH in mediating vascular contraction in HS-fed A2AAR−/− mice. Springer Science+Business Media New York, 2015 High salt nationallicence A2AAR nationallicence PPARγ nationallicence EETs nationallicence KATP channel nationallicence Soluble epoxide hydrolase nationallicence Pradhan Isha Department of Physiology & Pharmacology/Department of Basic Pharmaceutical Sciences, Center for Cardiovascular and Respiratory Sciences, School of Medicine/School of Pharmacy, West Virginia University, Biomedical Research Building, 2nd Floor, Room # 220, 3051 Health Science Center - North 1 Medical Center Drive, P. O. Box 9229, 26506-9229, Morgantown, WV, USA aut Ledent Catherine IRIBHN, Universite Libre de Bruxelles, 1070, Brussels, Belgium aut Mustafa S. Department of Physiology & Pharmacology/Department of Basic Pharmaceutical Sciences, Center for Cardiovascular and Respiratory Sciences, School of Medicine/School of Pharmacy, West Virginia University, Biomedical Research Building, 2nd Floor, Room # 220, 3051 Health Science Center - North 1 Medical Center Drive, P. O. Box 9229, 26506-9229, Morgantown, WV, USA aut Morisseau Christophe Department of Entomology and UC Davis Cancer Center, University of California, Davis, CA, USA aut Nayeem Mohammed Department of Physiology & Pharmacology/Department of Basic Pharmaceutical Sciences, Center for Cardiovascular and Respiratory Sciences, School of Medicine/School of Pharmacy, West Virginia University, Biomedical Research Building, 2nd Floor, Room # 220, 3051 Health Science Center - North 1 Medical Center Drive, P. O. Box 9229, 26506-9229, Morgantown, WV, USA aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 404/1-2(2015-06-01), 87-96 0300-8177 404:1-2<87 2015 404 11010 https://doi.org/10.1007/s11010-015-2368-4 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2368-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Pradhan Isha Department of Physiology & Pharmacology/Department of Basic Pharmaceutical Sciences, Center for Cardiovascular and Respiratory Sciences, School of Medicine/School of Pharmacy, West Virginia University, Biomedical Research Building, 2nd Floor, Room # 220, 3051 Health Science Center - North 1 Medical Center Drive, P. O. Box 9229, 26506-9229, Morgantown, WV, USA aut NATIONALLICENCE 700 1- Ledent Catherine IRIBHN, Universite Libre de Bruxelles, 1070, Brussels, Belgium aut NATIONALLICENCE 700 1- Mustafa S. Department of Physiology & Pharmacology/Department of Basic Pharmaceutical Sciences, Center for Cardiovascular and Respiratory Sciences, School of Medicine/School of Pharmacy, West Virginia University, Biomedical Research Building, 2nd Floor, Room # 220, 3051 Health Science Center - North 1 Medical Center Drive, P. O. Box 9229, 26506-9229, Morgantown, WV, USA aut NATIONALLICENCE 700 1- Morisseau Christophe Department of Entomology and UC Davis Cancer Center, University of California, Davis, CA, USA aut NATIONALLICENCE 700 1- Nayeem Mohammed Department of Physiology & Pharmacology/Department of Basic Pharmaceutical Sciences, Center for Cardiovascular and Respiratory Sciences, School of Medicine/School of Pharmacy, West Virginia University, Biomedical Research Building, 2nd Floor, Room # 220, 3051 Health Science Center - North 1 Medical Center Drive, P. O. Box 9229, 26506-9229, Morgantown, WV, USA aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 404/1-2(2015-06-01), 87-96 0300-8177 404:1-2<87 2015 404 11010