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.