Time‐dependent Alterations in Right Coronary Endothelial Function During the Development of Monocrotaline (MCT)‐induced Pulmonary Hypertension (PH) and Right Ventricular Hypertrophy (RVH) in Rats

We investigated the coronary endothelial (EC) changes during the development of MCT‐induced PH and RVH. Significant PH and RVH did not occur until 3 weeks after 60 mg/kg MCT injection (34±4 mmHg vs. 19±2 mmHg and 40±2% septum plus LV weight vs. 25±1% in controls, respectively). Coronay EC function at 1 day post‐MCT injection was studied to evaluate the direct chemical injury of MCT to EC. 1 and 3 weeks post‐MCT were to illustrate EC changes at pre‐ and post‐PH state, respectively. Isolated right coronary artery (RCA) response to acetylcholine (Ach)‐induced NO dilation was not altered 1 day after MCT, but progressively and significantly decreased after 1 and 3 weeks(Figure 1). Septal coronary arteries (SCA) showed a similar, but smaller, decrease in Ach dilation in 1 and 3 weeks MCT rats. No significant change was found in left coronaries (LCA). L‐NAME induced constriction, an estimate of the spontaneous EC NO mediated dilation, was not significantly altered in any of the MCT‐treated SCA and LCA, but was increased in the RCA after 1 week (−41±6%) and decreased after 3 weeks MCT (−18±3% vs. −27±3% in controls). A marked enhancement to 30 nM U46619 ‐induced constriction was also in the 3‐week RCA, but not the 1‐week. Sodium nitroprusside‐induced dilation was not different between the control and MCT rats. In summary, our findings showed that a selective and time‐dependent alteration in the right, but not left, coronary endothelial function is associated with and actually precedes the development of MCT‐induced pulmonary hypertension and right heart hypertrophy in rats. Possible molecular mechanisms and preservation of endothelial function as a new therapeutic target for RVH management are currently under investigation. 1