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 beta-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 (Fdia) remained increased and developed force (Fdev) 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 Fdia was significantly smaller, and recovered better while Fdev 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.