Gatti P J, Gertner S B
Neuropharmacology. 1984 Jun;23(6):663-70. doi: 10.1016/0028-3908(84)90148-5.
Bilateral injection of the inhibitor of histamine-N-methyltransferase, SKF 91488, which is also known as homodimaprit (5 micrograms), into the preoptic area of the rat produced delayed hypertension, tachycardia and hyperthermia. Some animals exhibited pulmonary edema. These effects were only noted 18-24 hr after an injection and were not an artifact of the injection, since the administration of artificial cerebrospinal fluid produced none of these effects. At the time noted, lesions of the rostral hypothalamus, including the preoptic area, were evident. Injection of a vasopressin antagonist, intravenously, did not lower the blood pressure of the hypertensive animals nor did previous bilateral adrenal demullation prevent or delay the hypertension or tachycardia. Therefore, it does not appear that hypersecretion of either vasopressin or adrenal catecholamines contributed to the cardiovascular effects. Peripheral pretreatment with the sympathetic neurotoxin 6-hydroxydopamine however, did prevent the delayed rise in blood pressure following an injection of homodimaprit. From these studies, it is concluded that the injection of homodimaprit produces lesions in the preoptic area, resulting in hypertension that is maintained by excessive activation of the sympathetic nervous system.
向大鼠视前区双侧注射组胺 - N - 甲基转移酶抑制剂SKF 91488（也称为高剂量二甲双胍，5微克），会导致迟发性高血压、心动过速和体温过高。一些动物出现了肺水肿。这些效应仅在注射后18 - 24小时才被观察到，且并非注射造成的假象，因为注射人工脑脊液并未产生这些效应。在观察到这些效应时，包括视前区在内的下丘脑前部出现了损伤。静脉注射血管加压素拮抗剂并不会降低高血压动物的血压，双侧肾上腺预先切除也不能预防或延缓高血压或心动过速。因此，血管加压素或肾上腺儿茶酚胺分泌过多似乎并未导致这些心血管效应。然而，用交感神经毒素6 - 羟基多巴胺进行外周预处理确实能预防注射高剂量二甲双胍后血压的延迟升高。从这些研究可以得出结论，注射高剂量二甲双胍会对视前区造成损伤，导致高血压，这种高血压是由交感神经系统的过度激活维持的。
