Development of tolerance to nitroglycerin in the arterial and venous circulation of dogs

The purpose of this study was to define the effects of nitroglycerin on venous tone and to investigate the time course of nitroglycerin tolerance in the peripheral circulation. The changes in the arterial and venous circulation resulting from an intravenous infusion of nitroglycerin (5 μg/kg per min) after 5 minutes (acute infusion) were compared with those changes that occurred after 2 hours (chronic infusion) of the same infusion in six splenectomized, ganglion-blocked dogs. Hemodynamics, blood volume and venous and arterial compliance were measured during each infusion. Nitroglycerin initially decreased mean arterial pressure from 81.5 ± 2.0 to 57.6 ± 2.7 mm Hg (p < 0.01). Central blood volume decreased from 21.1 ± 1.4 to 15.9 ± 1.1 ml/kg (p < 0.01), while total blood volume and unstressed vascular volume did not change. In the acute study, nitroglycerin increased venous compliance 33% from 1.75 ± 0.14 to 2.32 ± 0.16 ml/mm Hg per kg (p < 0.01) and arterial compliance 33% from 0.049 ± 0.007 to 0.065 ± 0.007 ml/mm Hg per kg (p < 0.01). At the end of the 2 hour infusion, arterial pressure increased and was now unchanged from control. Central blood volume had returned to baseline, 17.8 ± 0.9 ml/kg. Total blood volume and unstressed vascular volume remained unchanged. With the long-term infusion, both arterial and venous compliance decreased (p < 0.02) to 0.050 ± 0.006 and 1.50 ± 0.06 ml/mm Hg per kg, respectively, such that neither value was different from control. Nitroglycerin levels remained constant throughout. Thus, acute administration of nitroglycerin causes arterial and venous dilation by increasing compliance in each vascular bed. The duration of this response is shortlived with the development of tolerance within 2 hours.