Abstract
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 doseresponse experiments were conducted in vivo on normal control and high-fat-fed prediabetic dogs. Additionally, isolated left circumflex (LCX) coronary arteries and arterioles (<160 μm) 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 ETA receptor transcript levels in LCX coronary arteries and arterioles. Also, Western blotting revealed a significant decrease in ETA receptor protein in LCX coronary arteries. Conclusions: The findings of the present investigation indicate that although ETA 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.
Original language | English |
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Pages (from-to) | 209-218 |
Number of pages | 10 |
Journal | Microcirculation |
Volume | 13 |
Issue number | 3 |
DOIs | |
State | Published - Apr 2006 |
Keywords
- Coronary blood flow
- Endothelin-1
- Microcirculation
- Obesity