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.
Knudson
Jarrod D
JD
Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
Rogers
Paul A
PA
Dincer
U Deniz
UD
Bratz
Ian N
IN
Araiza
Alberto G
AG
Dick
Gregory M
GM
Tune
Johnathan D
JD
D000818:Animals; D001160:Arterioles / Q000503:physiopathology; D003331:Coronary Vessels / Q000503:physiopathology*; D004285:Dogs; D019332:Endothelin-1 / Q000494:pharmacology*; D024821:Metabolic Syndrome / Q000503:physiopathology*; D011236:Prediabetic State / Q000503:physiopathology; D044022:Receptor, Endothelin A / Q000032:analysis / Q000235:genetics; D014661:Vasoconstriction / Q000187:drug effects; D014666:Vasomotor System / Q000187:drug effects*
D019332:Endothelin-1; D044022:Receptor, Endothelin A