thromboxane-b2 and monocrotaline-pyrrole

Monocrotaline pyrrole (MCTP) causes pulmonary vascular injury and pulmonary hypertension in rats. Although the mechanism by which MCTP causes pulmonary hypertension is unknown, vasoconstriction may play a role. Thromboxane (Tx) A2 is a vasoconstrictor released from platelets and other blood cells. Following treatment with MCTP in vivo, the release of stable metabolites of TxA2 and prostacyclin [TxB2 and 6-keto prostaglandin F1 alpha (6-keto-PGF1 alpha), respectively] was determined in isolated lungs perfused with blood. Early in the development of pulmonary hypertension, the concentrations of TxB2 and 6-keto-PGF1 alpha in the effluent plasma of lungs from treated rats were not different from control rats. When pulmonary hypertension was well established, the concentration of TxB2 was higher in the effluent plasma of lungs from MCTP-treated rats, although the concentration of 6-keto-PGF1 alpha was not affected by treatment.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Hypertension, Pulmonary; Lung; Male; Monocrotaline; Pyrrolizidine Alkaloids; Rats; Thromboxane B2

Monocrotaline pyrrole (MCTP), a metabolite of the plant toxin monocrotaline, produces pulmonary vascular injury, pulmonary hypertension, and right ventricular enlargement (RVE) in rats by an unknown mechanism. A role for platelets has been suggested by the observation that antibody-induced thrombocytopenia reduces the RVE caused by MCTP. The platelet can release a number of vasoconstrictive agents, such as 5-hydroxytryptamine (5HT) and thromboxane A2 (TxA2), that could possibly contribute to pulmonary hypertension. It was of interest to determine whether treatment with MCTP alters platelet 5HT content or alters the release of TxA2 in platelet-rich plasma (PRP) in response to aggregation. Fourteen days following treatment with MCTP when pulmonary hypertension is well-established and RVE is present, the concentration of 5HT in washed platelets or in platelet-poor plasma was not different in treated and control rats. One day following treatment with MCTP, before lung injury is evident, the concentration of TxB2, a stable metabolite of TxA2, was higher in unstimulated PRP from treated rats than in control rats. The concentration of TxB2 was also examined in PRP at 4 days (when lung injury first appears), 7 days (when pulmonary arterial pressure first increases), and 14 days after treatment with MCTP (when RVE is evident). At 4, 7, or 14 days following treatment there was no difference in the concentration of TxB2 in unstimulated PRP from MCTP-treated and control rats. Following stimulation with arachidonic acid, the release of TxB2 at maximal aggregation was not different in PRP from MCTP-treated and control rats at any time after treatment. The rate of release of TxB2 was lower in PRP from rats treated with MCTP 7 days earlier, but was not different at any other time following treatment. At concentrations up to 250 micrograms/ml, MCTP added in vitro to PRP from untreated rats did not affect the concentration of TxB2 released during aggregation induced by arachidonic acid. Only at very high concentrations (1 mg/ml) did MCTP abolish the aggregation response and depress TxB2 release in PRP. These results indicate that MCTP treatment does not affect platelet 5HT content and does not affect basal TxB2 production or TxB2 release by platelets stimulated in vitro.

Topics: Animals; Blood Platelets; Hypertension, Pulmonary; Male; Monocrotaline; Platelet Aggregation; Pyrrolizidine Alkaloids; Rats; Rats, Inbred Strains; Serotonin; Thromboxane B2; Thromboxanes; Time Factors