Coronary Vasomotor Reactivity to Endothelin‐1 in the Prediabetic Metabolic Syndrome

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.