Endogenous vascular endothelial growth factor tonically sustains myocardial performance and cardiac vagal baroreflex as revealed by Flk‐1 deficient mice (681.1)

Abstract

Whereas the role of vascular endothelial growth factor (VEGF) in vascular functions is well‐known, its action on heart functions is relatively wanting. In this study, we sought to demonstrate that endogenous VEGF tonically sustains myocardial performance and cardiac vagal baroreflex via Flk‐1. Echocardiography showed that compared to wild‐type mice, Flk‐1 deficient Kdr+/‐ mice exhibited significantly reduced ejection fraction and fraction shortening; alongside significant diurnal hypertension and tachycardia as revealed by radiotelemetry. 24‐h on‐line, real‐time power spectral analysis further showed significant decrease in heart rate variability and indices of spontaneous cardiac vagal baroreflex in Kdr+/‐ mice. Tractographic analysis based on MRI/DTI revealed that the robust functional connectivity between the nucleus tractus solitarii (NTS) and nucleus ambiguus was significantly decreased in Kdr+/‐ mice. Furthermore, the reduced myocardial performance and cardiac vagal baroreflex in Kdr+/‐ mice were exacerbated during neurogenic hypertension induced by i.c.v infusion of angiotensin II. We concluded that the endogenous VEGF sustains cardiac functions either by acting directly on Flk‐1 in the heart, or indirectly by affecting the cardiac vagal baroreflex via Flk‐1 in the NTS. This tonic modulatory mechanism is crucial to myocardial performance under neurogenic hypertension.