Vascular reactivity and permeability to serotonin in cyclooxygenase-inhibited dog lung

We examined the effects of serotonin (5-HT) infusion on hemodynamics, vascular compliance (Cvasc), and the filtration coefficient (Kf) in the isolated canine lower left lung lobe (LLL) perfused at constant flow. In one group (5-HT; n = 8), 5-HT was infused at 55 micrograms/min for 35 min and then at 105 micrograms/min for 15 min before and during a Kf determination. Cyclooxygenase inhibition (COI) was induced by 40 microM indomethacin (n = 4) or 45 microM meclofenamate (n = 4) before 5-HT infusion in a second group (5-HTCOI; n = 8). Control LLLs (n = 8) were given equivalent volumes of saline. The pulmonary arterial pressure (Pa) increase to 55 micrograms/min 5-HT (3.0 +/- 0.6 Torr; 43.7%) was nearly doubled (P less than 0.01) with COI (10.5 +/- 1.5 Torr; 83.3%), while LLL weight decreased 6.2 g/100 g in both groups. With 5-HT infusion, the dose-dependent increase in Pa, lobar vascular resistance, and precapillary resistance was greater (P less than 0.05) in the 5-HTCOI than the 5-HT group, but capillary pressure (Pc) was not increased from base-line values. Kf values did not differ (P greater than 0.05) among groups but Cvasc was reduced (P less than 0.05) in the 5-HTCOI group. We found that 5-HT increases Pa, but does not appear to promote microvessel fluid filtration by increasing Pc or the Kf. The enhanced and sustained pressor response to 5-HT with COI suggests that vasodilatory prostaglandins may modulate pressor responses to 5-HT.