Background In isolated mammalian cardiomyocytes, papillary muscle preparations, and ejecting hearts, nitric oxide (NO) or other cyclic GMP-elevating interventions increase diastolic cell length and reduce peak contractile performance by hastening onset of myocardial relaxation. In the present study, the effect of NO on left ventricular (LV) relaxation and diastolic distensibility was investigated in humans.Methods and Results The NO donor substance sodium nitroprusside was infused during cardiac catheterization in the global coronary bed of the LV of patients (n=13) investigated for chest pain who were without evidence of obstructive coronary artery or other cardiac disease.Sodium nitroprusside was infused intracoronarily at a dosage (<=4 micrograms/min) that was previously shown to be devoid of systemic effects when infused into the brachial artery to investigate the reactivity of the forearm vascular bed. The effect of this global intracoronary infusion of the NO donor sodium nitroprusside was assessed by sequential LV angiograms and tip-micromanometer pressure recordings. During global intracoronary nitroprusside infusion, there was a decrease in heart rate from 78+-11 to 76+-12 beats per minute (P<.05), in LV peak systolic pressure from 161+-18 to 146+-18 mm Hg (P<.001), and in time to onset of LV relaxation (interval from Q wave on the ECG to LV dP/dtmin) from 432+-36 to 419+-36 milliseconds (P<.01). In 7 patients in whom adequate sequential LV angiograms could be obtained, LV end-diastolic volume increased from 158+-34 to 165+-40 mL (P<.05), whereas LV end-diastolic pressure fell from 18+-5 to 12+-3 mm Hg (P<.02), and in 5 of these 7 patients, a downward shift of the diastolic LV pressure-volume relation was observed. In 5 patients, a right atrial infusion of sodium nitroprusside was performed either before (n=2) or after the global intracoronary infusion. The decrease in LV peak systolic pressure observed during right atrial infusion was significantly smaller (P<.01) than during global intracoronary infusion.Conclusions The present study reveals reduced LV pressure development, an LV relaxation-hastening effect, and improved LV diastolic distensibility during global intracoronary infusion of the NO donor substance sodium nitroprusside. These effects appeared to be unrelated to systemic vasodilation or to pericardial constraint and could be explained by a direct myocardial effect of NO, probably through activation of guanylyl cyclase to increase cyclic GMP or through modification of other cellular proteins. (Circulation. 1994;89:2070-2078.)