Increases in circulating atrial natriuretic peptide (ANP) and norepinephrine (NE) occur during the evolution of heart failure. While NE may augment ANP synthesis, a modulating action upon the biological actions of ANP is unclear. In vitro, the beta-adrenergic agonist (βA) isoproterenol (ISO) down-regulates the AN Pclearance receptor which indirectly augments the biologically active ANP receptor. In vivo, the βA antagonist propranolol attenuates natriuretic peptide mediated coronary vasodilatation. We therefore hypothesized that, in vivo, ISO would potentiate subthreshold coronary vasodilating actions of ANP. Five anesthetized dogs were instrumented to measure left circumflex (LCx) coronary blood flow (CBF). Intracoronary (IC) ANP (100 nglbolus) was administered in the LCx before and after the IC-ISO (1mg over 15min). Acetylcholine (ACh 1nglkg) and sodium nitroprusside (SNP 100nglkg) were administered to determine the influence of ISO on endothelial dependent and independent vasodilatation. In the control state (*p<0.05). both IC-ACh and IC-SNP resulted in marked coronary vasodilatation (▵ CBF ACh 76±6*mllmin and SNP 37±7*) while IC-ANP did not alter CBF. IC-ISO increased basal CBF (52±11 ml/min to 87±21*) and LV contractility (+dP/dt 1803±93mmHgL/sec to 2395±151*). and decreased coronary vascular resistance (CVR 2.6±0.3 RU to 1.4±0.2*) and coronary perfusion pressure (105±7mmHg to 87±7*). In the presence of ISO, IC-ANP significantly increased CBF (87±21ml/min to 117±26*) while ACh and SNP-mediated coronary vasodilation were similar to control changes.In summary, IC-ISO augments ANP-mediated coronary vasodilatation but does not enhance ACh or SNP mediated vasodilatation. This observation suggests a functional link between the natriuretic peptide system and the β-adrenergic system in the control of CBF. The elevation in circulating catecholamines observed in CHF may, therefore, serve in part to augment endogenous ANP-mediated coronary vasodilation and thus be coronary protective in the progression of CHF.