In heart failure (CHF), coronary vascular relaxation is associated with endothelial dysfunction and nitric oxide (NO) deficiency. This study explored the reversibility of this process in hearts recovering from CHF and its related mechanisms. Dogs were chronically instrumented to measure cardiac function and coronary blood flow (CBF). Heart failure was induced by right ventricular pacing at 240 bpm for 3-4 weeks, and cardiac recovery (CR) was allowed by the termination of cardiac pacing for 3-4 weeks following the development of CHF, in which LV contractile function was restored by 80-90%. The endothelium-dependent CBF response to bradykinin and acetylcholine was depressed in CHF and fully restored in CR. Myocardial NOx, eNOS mRNA expression, total protein, and phosphorylated eNOS decreased significantly in failing hearts. However, myocardial NOx recovered to 78% of control and phosphorylated eNOS was fully restored in CR, despite that eNOS mRNA expression and protein levels remained lower than control. Furthermore, the endothelium-independent CBF response to nitroglycerine did not change in CHF, however, it increased by 75% in CR, in conjunction with a near 3-fold increase in the phosphorylation of vasodilation-stimulated phosphoprotein (VASP) at Ser²³⁹ in recovering hearts. Thus, the complete restoration of endothelium-dependent coronary vascular relaxation during cardiac recovery from CHF was mediated by (1) a restoration of phosphorylated eNOS for partially recovery of the NO production, and (2) an increase in the cGMP/cGK-I pathway signaling activity for the enhancement of coronary vascular smooth muscle relaxation in response to NO.