Transient and sustained impacts of hydroxyl radicals on sarcoplasmic reticulum function: protective effects of nebivolol

Abstract

The hydroxyl radical ( ·OH) is a very reactive oxygen-free radical species that has profound effects on myocardial contractility. We investigated the impact of ·OH on free radical induced injury in right ventricular rabbit cardiac trabeculae. Additionally, we investigated the protective properties of the β-adrenoceptor antagonist nebivolol. The contractile response to a brief, 2 min exposure to ·OH consisted of a severe but transient rigor-like contracture, followed by a new steady state in which diastolic force ( F dia) remained increased and developed force ( F dev) remained decreased. In the new steady state sarcoplasmic reticulum function only partly recovered, reflected by a >50% blunted force–frequency relationship. In the presence of nebivolol (10 −6 M), during the early phase the increase in F dia was significantly smaller, and recovered better while F dev was higher during peak. Moreover, nebivolol completely abolished blunting of the force–frequency relationship, which was observed in the sustained ·OH injury phase. The results indicate that hydroxyl radical injury induces systolic and diastolic dysfunction, and that nebivolol can effectively prevent a large part of this ·OH injury.