Inhibition of endogenous nitric oxide synthase augments contractile response to adenylyl cyclase stimulation without altering mechanical efficiency in patients with idiopathic dilated cardiomyopathy.

BACKGROUND Increased nitric oxide (NO) in the failing heart attenuates the myocardial contractile response to beta-adrenergic receptor stimulation. However, the physiological effects of NO on the beta-adrenergic post-receptor signaling system are unknown. The objective of the present study was to examine the effects of cardiac NO synthase (NOS) inhibition on left ventricular (LV) hemodynamics and mechanoenergetics in response to adenylyl cyclase stimulation in human heart failure. METHODS AND RESULTS The study group comprised 13 patients with heart failure because of idiopathic cardiomyopathy (IDC). Emax was examined as an index of LV contractility, LV external work (EW), pressure-volume area (PVA), myocardial oxygen consumption (MVO2), and mechanical efficiency (EW/MVO2) with the use of conductance and coronary sinus thermodilution catheters before and during colforsin daropate infusion, and during concurrent infusion of colforsin daropate with the NOS inhibitor, NG-monomethyl-L-arginine (L-NMMA; 200 micromol). Colforsin daropate increased Emax by 53% and EW by 18%, and reduced PVA by 14%, without altering MVO2 or mechanical efficiency. The combination of colforsin daropate with L-NMMA further increased Emax by 26% and reduced PVA by 9%, without altering MVO2 or mechanical efficiency. CONCLUSIONS These findings suggest endogenous NO may modulate beta-adrenergic post-receptor pathways and preserve myocardial efficiency in patients with IDC.