Abstract P523: Time and Concentration Dependent Vascular Changes of Cancer Therapy Everolimus in Mesenteric Resistance Arteries [Session Title: Vascular]

The leading cause of death in cancer survivors is cardiovascular disease, in part due to cancer therapy-induced cardiotoxicity. The short- and long-term cardiovascular side effects of a newer class of targeted chemotherapy, mTOR inhibitors, have not been well established as they have been with anthracyclines, anti-VEGF therapy and tyrosine kinase inhibitors. mTOR inhibitor Everolimus, used as an agent in transplant immunosuppression, is now indicated for the treatment of metastatic breast, colon, renal cell and pancreatic cancer. Retrospective clinical data indicate the possibility of heart failure and hypertension as cardiotoxic effects of Everolimus, although data are inconclusive and no vascular function studies are available. We studied the effects of Everolimus on the contractility and relaxation of mesenteric resistance arteries (MRA) of male Wistar rats (12-15 weeks old) at different drug incubation time frames (1, 12, and 24 hours) on a tension wire myograph. We hypothesized that the longer exposure to Everolimus (i.e. longer incubation time) leads to enhanced contractility to phenylephrine (PE) and impaired relaxation to acetylcholine (ACh). Two concentrations of Everolimus were evaluated, 0.1 μM and 0.1 nM. MRA exposed to Everolimus 0.1 μM showed a decreased contractile response to PE at 1 hour incubation (LogEC50, Ctrl: -5.627±0.07 vs. Drug: -5.390±0.10, *p=0.03) and at 12 hours incubation (LogEC50, Ctrl: -5.295±0.16 vs. Drug: -5.645±0.08, *p=0.04), while no ...
Source: Hypertension - Category: Cardiology Authors: Tags: Poster Abstract Presentations Source Type: research