Cardiovascular effects of a herbicide containing glufosinate and a surfactant: in vitro and in vivo analyses in rats.
A herbicide, Basta (BASTA), containing glufosinate ammonium (GLA) as the main component and an anionic surfactant, sodium polyoxyethylene alkylether sulfate (AES), causes hemodynamic changes characterized by a decrease in total vascular resistance with an increase or a decrease in cardiac output in human acute oral poisoning. With a motivation based on these clinical observations, we tried to elucidate the exact component and its mode of action that is mostly responsible for the direct cardiovascular effects of this herbicide formulation, investigating the effects of BASTA, GLA, and AES independently on the cardiovascular system in rats in vitro and in vivo. In isolated right atria beating spontaneously in Krebs-Ringer's solution, BASTA and AES produced negative chronotropic responses in a concentration-dependent manner. In electrically driven isolated left atria, BASTA and AES produced positive inotropic responses concentration dependently but negative inotropic responses at extremely high concentrations. In aortic ring segments, BASTA and AES produced no vasoconstrictive effects but exerted significant vasodilative effects when the aortic ring was precontracted with phenylephrine. These in vitro responses caused by BASTA and AES occurred to a similar degree. On the other hand, the main component, GLA, produced no effects in isolated atria and aortas. In anesthetized rats, relatively low doses of BASTA and AES produced a decrease in blood pressure followed by a slight increase in heart rate, which was presumably due to baroreflex caused by the decrease in blood pressure. At an extremely high dose, BASTA and AES produced a decrease in blood pressure with a marked decrease in heart rate. These in vivo responses to BASTA and AES also occurred to a similar degree. In contrast, the main component, GLA, did not produce any effects on heart rate and blood pressure in anesthetized rats. From these results, we concluded that the effects of BASTA in our in vivo experiments were not caused by the main component, GLA, but was mostly caused by AES through its vasodilative effects plus cardiostimulatory effects at low doses and cardiosuppressive effects at high doses.
Koyama
K
K
Department of Emergency Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
Koyama
K
K
Goto
K
K
D000613:Aminobutyrates / Q000633:toxicity*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D005974:Glutamate-Ammonia Ligase / Q000037:antagonists & inhibitors; D006325:Heart Atria / Q000187:drug effects; D006540:Herbicides / Q000633:toxicity; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D011092:Polyethylene Glycols / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013501:Surface-Active Agents / Q000633:toxicity*
D000613:Aminobutyrates; D006540:Herbicides; D013501:Surface-Active Agents; D011092:Polyethylene Glycols; C003121:phosphinothricin; D005974:Glutamate-Ammonia Ligase