Effect of aspirin on vascular tone and reactivity to vasoactive amines in the dog lung

The effect of increasing blood levels of aspirin on pulmonary hemodynamics and pressor response to vasoactive amines was examined in the isolated canine lung lobe, blood perfused at constant flow. At steady state lobar vascular resistance (LVR), lobes were challenged with either 250 micrograms serotonin (5-HT; n = 4), 5.0 mumol acetylcholine (ACh; n = 4) or 50 micrograms norepinephrine (NE; n = 4) before and after blood aspirin concentration [ASA] was incrementally increased from 17 to 3140 microM. LVR was partitioned into arterial (Ra) and venous (Rv) segments by venous outflow occlusions 20 min after each ASA addition and at the peak of the pressor response to each amine. ASA treatment was associated with a dose-related 105% increase in LVR (P < 0.01) accounted for by a 154% increase in Ra (P < 0.01) and a 70% increase in Rv (P < 0.01) at 3150 microM ASA (n = 12). In spite of increased vascular tone, higher [ASA] also potentiated increases in both pulmonary arterial pressure and LVR to both 5-HT and NE whereas only Ra increased with ACh challenge. Thus, the increase in pulmonary vascular tone and reactivity to vasoactive amines is positively correlated with blood aspirin levels in the dog.