Wilkinson M F, Kasting N W
Department of Physiology, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Am J Physiol. 1989 May;256(5 Pt 2):R1164-8. doi: 10.1152/ajpregu.1989.256.5.R1164.
Central microinjection or infusion of an arginine vasopressin (AVP) V1-receptor antagonist within the brain of the conscious, unrestrained, and febrile rat inhibited or abolished the antipyretic effects of peripherally administered indomethacin (Indo). The degree of Indo-induced antipyresis was determined by 2-h thermal indexes (degree C.h) calculated from the time of Indo injection. Microinjection of saline or V1-receptor antagonist within the ventral septal area (VSA) of the rat brain immediately followed by intraperitoneal Indo evoked antipyretic responses of -1.63 +/- 0.17 and -0.24 +/- 0.09 degrees C.h, respectively (P less than 0.01). Infusion of the VSA with saline or V1-receptor antagonist before and after Indo resulted in thermal indexes of -1.35 +/- 0.16 and 0.13 +/- 0.30 degree C.h, respectively (P less than 0.01). Central microinjection of a V2-receptor antagonist did not significantly effect Indo-induced antipyresis compared with paired saline controls. Neither saline nor the V1-receptor antagonist affected nonfebrile body temperature when microinjected into the VSA. These data indicate the importance of AVP V1-receptors within the VSA in mediating the potent fever-reducing properties of the antipyretic drug Indo. Furthermore, these data call into question whether prostaglandin synthesis inhibition is a sufficient explanation of drug-induced antipyresis.
在清醒、未受束缚且发热的大鼠脑内中央微量注射或输注精氨酸加压素（AVP）V1受体拮抗剂，可抑制或消除外周给予吲哚美辛（Indo）的解热作用。Indo诱导的解热程度由注射Indo后2小时的热指数（℃·小时）确定。在大鼠脑腹侧隔区（VSA）微量注射生理盐水或V1受体拮抗剂后立即腹腔注射Indo，分别引起-1.63±0.17和-0.24±0.09℃·小时的解热反应（P<0.01）。在Indo给药前后向VSA输注生理盐水或V1受体拮抗剂，热指数分别为-1.35±0.16和0.13±0.30℃·小时（P<0.01）。与配对的生理盐水对照组相比，中央微量注射V2受体拮抗剂对Indo诱导的解热作用无显著影响。向VSA微量注射生理盐水或V1受体拮抗剂均不影响非发热体温。这些数据表明VSA内的AVP V1受体在介导解热药物Indo的强效退热特性中具有重要作用。此外，这些数据质疑前列腺素合成抑制是否足以解释药物诱导的解热作用。
