OBJECTIVE: The purpose of the present investigation was to test the hypothesis that coronary vasoconstrictor responses to endothelin-1 are augmented in the prediabetic metabolic syndrome. METHODS: ELISA was used to measure plasma endothelin-1 and intracoronary endothelin-1 dose-response experiments were conducted in vivo on normal control and high-fat-fed prediabetic dogs. Additionally, isolated left circumflex (LCX) coronary arteries and arterioles (< 160 microm) were used for in vitro functional studies and molecular analyses (quantitative real-time PCR and Western blotting). RESULTS: Plasma endothelin-1 concentrations were not different between control and prediabetic dogs. Coronary vasoconstriction to endothelin-1 was similar in control and prediabetic dogs, both in vivo and in isolated arterioles. Nonetheless, real-time PCR analysis revealed significant decreases in ET(A) receptor transcript levels in LCX coronary arteries and arterioles. Also, Western blotting revealed a significant decrease in ET(A) receptor protein in LCX coronary arteries. CONCLUSIONS: The findings of the present investigation indicate that although ET(A) receptor-signaling is sensitized by induction of the metabolic syndrome, endothelin-mediated coronary vasoconstriction does not significantly contribute to coronary dysfunction at this early stage of prediabetes.
OBJECTIVE: The purpose of the present investigation was to test the hypothesis that coronary vasoconstrictor responses to endothelin-1 are augmented in the prediabetic metabolic syndrome. METHODS: ELISA was used to measure plasma endothelin-1 and intracoronary endothelin-1 dose-response experiments were conducted in vivo on normal control and high-fat-fed prediabetic dogs. Additionally, isolated left circumflex (LCX) coronary arteries and arterioles (< 160 microm) were used for in vitro functional studies and molecular analyses (quantitative real-time PCR and Western blotting). RESULTS: Plasma endothelin-1 concentrations were not different between control and prediabetic dogs. Coronary vasoconstriction to endothelin-1 was similar in control and prediabetic dogs, both in vivo and in isolated arterioles. Nonetheless, real-time PCR analysis revealed significant decreases in ET(A) receptor transcript levels in LCX coronary arteries and arterioles. Also, Western blotting revealed a significant decrease in ET(A) receptor protein in LCX coronary arteries. CONCLUSIONS: The findings of the present investigation indicate that although ET(A) receptor-signaling is sensitized by induction of the metabolic syndrome, endothelin-mediated coronary vasoconstriction does not significantly contribute to coronary dysfunction at this early stage of prediabetes.
Authors: Léna Borbouse; Gregory M Dick; Gregory A Payne; Brittany D Payne; Mark C Svendsen; Zachary P Neeb; Mouhamad Alloosh; Ian N Bratz; Michael Sturek; Johnathan D Tune Journal: Am J Physiol Heart Circ Physiol Date: 2009-12-31 Impact factor: 4.733
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Authors: Zachary C Berwick; Gregory M Dick; Steven P Moberly; Meredith C Kohr; Michael Sturek; Johnathan D Tune Journal: J Mol Cell Cardiol Date: 2011-07-12 Impact factor: 5.000
Authors: Gregory A Payne; Léna Borbouse; Ian N Bratz; William C Roell; H Glenn Bohlen; Gregory M Dick; Johnathan D Tune Journal: Microcirculation Date: 2008-07 Impact factor: 2.628
Authors: Oana Sorop; Jens van de Wouw; Selena Chandler; Vahagn Ohanyan; Johnathan D Tune; William M Chilian; Daphne Merkus; Shawn B Bender; Dirk J Duncker Journal: Cardiovasc Res Date: 2020-03-01 Impact factor: 10.787