Chronic urotensin-II infusion induces diastolic dysfunction and enhances collagen production in rats

Abstract

The vasoactive peptide urotensin-II (U-II) is likely to play a key causal role in cardiac remodeling that ultimately leads to heart failure. Its contribution, specifically to the development of diastolic dysfunction and the downstream intracellular signaling, however, remains unresolved. This study interrogates the effect of chronic U-II infusion in normal rats on cardiac structure and function. The contribution of Rho kinase (ROCK) signaling to these pathophysiological changes is evaluated in cell culture studies. Chronic high-dose U-II infusion over 4 wk signifi-cantly impaired diastolic function in rats on echocardiography-derived Doppler indexes, including E-wave deceleration time (vehic..