Coronary vasodilation with nitrocompounds--is there a maximum?

The maximal extent of the dilation of epicardial coronary arteries attainable with nitro-compounds was investigated in 12 patients with coronary artery disease. Before and 5, 10, 15, 19, 60 and 64 min after onset of a 4-min-intravenous infusion of 0.025 mg SIN-1/kg bodyweight coronary angiograms were performed in identical projection; simultaneously, the mean pulmonary wedge pressure (PWP) was measured. At 15 and 60 min, 0.8 mg nitroglycerin (NTG) were additionally administered as sublingual spray. Mean diameters of angiographically normal coronary segments were analyzed with the computer-assisted contour detection system CAAS; they increased by an average maximum of 29 +/- 5% prior to NTG (p less than 0.001). PWP decreased from 9.2 +/- 3.1 mmHg to an average minimum of 4.3 +/- 1.6 mmHg (p less than 0.01) prior to NTG. Neither of these SIN-1-effects was significantly augmented by additional NTG: at 19 min coronary dilation amounted to 28 +/- 7% (p less than 0.001), PWP to 3.9 +/- 1.0 mmHg (p less than 0.01). At 60 min coronary dilation still amounted to 24 +/- 8% (p less than 0.001), PWP to 6.2 +/- 2.5 mmHg (p less than 0.05). By the second administration of NTG the maximal effects attained before could be reproduced: coronary dilation 28 +/- 8% (p less than 0.001), PWP 4.6 +/- 2.2 mmHg (p less than 0.01). Thus, the dilation reserve of epicardial coronary arteries for nitrocompounds is approximately 30% on average. These results suggest the possibility of a reproducible maximal activation of the enzyme guanylate cyclase which seems to be the mediator of the nitro-compound-induced vasodilation.