Thrombin and
thrombin receptor activation impact cardiomyocyte contraction and
ventricular remodeling. However, there is some controversy regarding their effects in cardiac function, especially in cardiac dysfunction after acute
myocardial infarction (AMI). A rat AMI model was created by left coronary artery
ligation (LCA). Cardiac functional parameters, including the maximum left ventricular (LV) systolic pressure (LVSPmax), LV end-diastolic pressure (LVEDP), and the rise and fall rates in LV pressure (dp/dt max and dp/dt min, respectively), were measured.
Hirudin decreased cardiac function within 120 minutes after AMI, whereas treatment with
thrombin receptor-activating peptide (TRAP) reversed this
hirudin-induced decrease in cardiac function. The
mRNA and
protein expression levels of
inositol 1,4,5-trisphosphate receptor (IP3R) subtypes in
infarct area tissues were analyzed by reverse transcription-polymerase chain reaction and immunoreaction.
Hirudin decreased the expression levels of IP3R-1, -2, and -3 in the
infarct area for up to 40 minutes after AMI, whereas TRAP treatment reversed these
hirudin-induced effects. Treatment with the IP3R antagonist
2-aminoethoxydiphenyl borate (2.5 mg/kg) eliminated the effect of TRAP on the
hirudin-induced decrease in cardiac function after AMI. Finally, TRAP increased the maximum binding capacity of the three IP3R subtypes, but only enhanced the affinity of IP3R-2.
Thrombin and
thrombin receptor activation improved cardiac function after AMI by an IP3R-mediated pathway, probably through the IP3R-2 subtype.