K. Koyama et al., CARDIOVASCULAR EFFECTS OF A HERBICIDE CONTAINING GLUFOSINATE AND A SURFACTANT - IN-VITRO AND IN-VIVO ANALYSES IN RATS, Toxicology and applied pharmacology, 145(2), 1997, pp. 409-414
A herbicide, Basta (BASTA), containing glufosinate ammonium (GLA) as t
he main component and an anionic surfactant, sodium polyoxyethylene al
kylether sulfate (AES), causes hemodynamic changes characterized by a
decrease in total vascular resistance with an increase or a decrease i
n cardiac output in human acute oral poisoning. With a motivation base
d on these clinical observations, we tried to elucidate the exact comp
onent and its mode of action that is mostly responsible for the direct
cardiovascular effects of this herbicide formulation, investigating t
he effects of BASTA, GLA, and AES independently on the cardiovascular
system in rats in vitro and in vivo. In isolated right atria beating s
pontaneously in Krebs-Ringer's solution, BASTA and AES produced negati
ve chronotropic responses in a concentration-dependent manner. In elec
trically driven isolated left atria, BASTA and AES produced positive i
notropic responses concentration dependently but negative inotropic re
sponses at extremely high concentrations. In aortic ring segments, BAS
TA and AES produced no vasoconstrictive effects but exerted significan
t vasodilative effects when the aortic ring was precontracted with phe
nylephrine. These in vitro responses caused by BASTA and AES occurred
to a similar degree. On the other hand, the main component, GLA, produ
ced no effects in isolated atria and aortas. In anesthetized rats, rel
atively low doses of BASTA and AES produced a decrease in blood pressu
re followed by a slight increase in heart rate, which was presumably d
ue to baroreflex caused by the decrease in blood pressure. At an extre
mely high dose, BASTA and AES produced a decrease in blood pressure wi
th a marked decrease in heart rate. These in vivo responses to BASTA a
nd AES also occurred to a similar degree. In contrast, the main compon
ent, GLA, did not produce any effects on heart rate and blood pressure
in anesthetized rats. From these results, we concluded that the effec
ts of BASTA in our in vivo experiments were not caused by the main com
ponent, GLA, but was mostly caused by AES through its vasodilative eff
ects plus cardiostimulatory effects at low doses and cardiosuppressive
effects at high doses. (C) 1997 Academic Press.