Cardiovascular responses to leukotriene C4 in the rat

Bolus injections of leukotriene C4, (LTC4; 0.1 to 10 micrograms/kg) were administered to anesthetized closed-chest rats i.v., before and min after administration of indomethacin (2 mg/kg). Systemic arterial pressure (SAP) and pulmonary arterial pressure (PAP) were monitored continuously. LTC4 produced dose-dependent changes in SAP and PAP. The characteristic SAP response to LTC4 (4 micrograms/kg) consisted of an initial transient rise (16 mm Hg), followed by a sustained decrease (18 mm Hg). LTC4 produced only a decrease in PAP (4 mm Hg). Cardiac output (CO) and heart rate (HR) were measured in the control period and during the maximum increase and decrease in SAP. Decreases in CO (32 ml/min) and HR (15 beats/min) occurred during the initial rise in SAP and further declined (36 ml/min and 21 beats/min, respectively) during the systemic hypotensive phase. Total peripheral resistance markedly increased during the transient rise in SAP (67%). Indomethacin potentiated the transient rise in SAP and attenuated systemic and pulmonary hypotensive responses induced by LTC4. Decreases in CO and HR induced by LTC4 were also attenuated by indomethacin, but total peripheral resistance was not significantly altered. These observations describe a characteristic hemodynamic response to LTC4 in the rat that reflects the composite actions of LTC4 as well as those of prostanoate compounds that may be synthesized and released after LTC4 administration.