Background
While β-adrenergic blockade is a cornerstone of heart failure therapy, its therapeutic role in chronic mitral regurgitation remains questionable. Animal studies and a small clinical trial have demonstrated cardiac functional improvement with β1-adrenoceptor blocker metoprolol in chronic mitral regurgitation [1, 2]. How β1AR-blockade halts functional decline of the volume-overloaded, eccentric hypertrophied heart is not well understood; anti-oxidant effects of β-blockade (βB) may play a role. We recently demonstrated that volume-overload cardiac stress induces re-localization and microdomain-specific oxidation of the nitric oxide receptor soluble guanylyl cyclase (sGC) in the failing heart [3, 4]. Given that nitric oxide-cyclic guanosine monophosphate (NO-cGMP) modulates cardiac contractility and protects against cardiac hypertrophy, we hypothesized that β1AR-blockade prevents oxidation of sGC and promotes myocardial NO-cGMP signaling in a microdomain-specific fashion.