Modulation of sympathetic coronary vasoconstriction by cardiac renin-angiotensin system in human coronary heart disease

Background-In humans, angiotensin II enhances the sympathetic coronary vaso constriction elicited by the cold presser test (CPT) and diving. Whether th is enhancement depends on the circulating angiotensin II or on the locally produced angiotensin II is unknown, however. Methods and Results-We addressed this issue in 14 patients with severe coro nary artery disease by evaluating the effects of a 2-minute CPT (n=14) and a 30-second dive (n=8) on mean arterial pressure (MAP, arterial catheter), heart rate (ECG), coronary sinus blood flow (CBF, thermodilution technique) , and coronary vascular resistance (MAP/CBF ratio). The 2 stimuli were appl ied at the end of left intracoronary infusion of either saline or benazepri lat diluted at the concentration of 25 mu g/mL. The rare of benazeprilat in fusion had been preliminarily demonstrated to reduce angiotensin II concent ration in the coronary sinus without affecting its arterial concentration. The changes in MAP and heart rate induced by CPT and diving were superimpos able during saline and benazeprilat infusions. The decrease in CBF induced by CPT and diving during saline infusion was changed into an increase durin g benazeprilat infusion with a significant attenuation of the coronary vaso constrictor response. Conclusions-In patients with coronary artery disease, an attenuation of sym pathetic coronary vasoconstriction can be obtained by reducing cardiac angi otensin II formation without involving circulating angiotensin II. This sug gests a role of the tissue renin-angiotensin system in modulating autonomic cardiac drive in humans.