5-Hydroxytryptamine and thromboxane in platelets from rats treated with monocrotaline pyrrole

Abstract

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 A 2 (TxA 2), 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 TxA 2 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 TxB 2, a stable metabolite of TxA 2, was higher in unstimulated PRP from treated rats than in control rats. The concentration of TxB 2 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 TxB 2 in unstimulated PRP from MCTP-treated and control rats. Following stimulation with arachidonic acid, the release of TxB 2 at maximal aggregation was not different in PRP from MCTP-treated and control rats at any time after treatment. The rate of release of TxB 2 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 μg/ml, MCTP added in vitro to PRP from untreated rats did not affect the concentration of TxB 2 released during aggregation induced by arachidonic acid. Only at very high concentrations (1 mg/ml) did MCTP abolish the aggregation response and depress TxB 2 release in PRP. These results indicate that MCTP treatment does not affect platelet 5HT content and does not affect basal TxB 2 production or TxB 2 release by platelets stimulated in vitro.