De Matteo Robert, Head Geoffrey A, Mayorov Dmitry N
Baker Heart Research Institute, P.O. Box 6492, St. Kilda Rd. Central, Melbourne, Victoria 8008, Australia.
Am J Physiol Regul Integr Comp Physiol. 2006 Jan;290(1):R257-64. doi: 10.1152/ajpregu.00372.2005. Epub 2005 Sep 1.
The dorsomedial hypothalamus (DMH) is critically implicated in the cardiovascular response to emotional stress. This study aimed to determine whether the DMH is also important in cardiovascular arousal associated with appetitive feeding behavior and, if so, whether locally released angiotensin II and glutamate are important in this arousal. Emotional (air-jet) stress and feeding elicited similar tachycardic (+51 and +45 beats/min, respectively) and pressor (+16 and +9 mmHg, respectively) responses in conscious rabbits. Bilateral microinjection of GABA(A) agonist muscimol (500 pmol) into the DMH, but not nearby hypothalamic regions, attenuated pressor and tachycardic responses to air-jet by 56-63% and evoked anorexia. Conversely, stimulation of the DMH with the glutamate analog kainic acid (250 pmol) elicited hypertension (+25 mmHg) and tachycardia (+114 beats/min) and activated feeding behavior. Local microinjection of a glutamate receptor antagonist, kynurenic acid (10 nmol), decreased pressor responses to stress and eating by 46 and 72%, respectively, without affecting feeding behavior. Bilateral microinjection of a selective AT(1)-receptor antagonist, candesartan (500 pmol), into the DMH, but not nearby sites, attenuated pressor and tachycardic stress responses by 31 and 33%, respectively. Candesartan did not alter feeding behavior or circulatory response to feeding. These results indicate that, in addition to its role in mediating stress responses, the DMH may be important in regulating cardiovascular arousal associated with feeding. Local glutamatergic inputs appear to regulate cardiovascular response to both stress and feeding. Conversely, angiotensin II, acting via AT1 receptors, may selectively modulate, in the DMH, cardiovascular response to stress, but not feeding.
下丘脑背内侧核(DMH)在情绪应激的心血管反应中起关键作用。本研究旨在确定DMH在与食欲性进食行为相关的心血管唤醒中是否也很重要,如果是,局部释放的血管紧张素II和谷氨酸在这种唤醒中是否重要。情绪(喷气)应激和进食在清醒兔中引发了相似的心动过速反应(分别为+51次/分钟和+45次/分钟)和升压反应(分别为+16 mmHg和+9 mmHg)。双侧向DMH而非附近下丘脑区域微量注射GABA(A)激动剂蝇蕈醇(500 pmol),可使对喷气的升压和心动过速反应减弱56%-63%,并诱发厌食。相反,用谷氨酸类似物 kainic 酸(250 pmol)刺激DMH会引发高血压(+25 mmHg)和心动过速(+114次/分钟)并激活进食行为。局部微量注射谷氨酸受体拮抗剂犬尿氨酸(10 nmol)分别使对应激和进食的升压反应降低46%和72%,而不影响进食行为。双侧向DMH而非附近部位微量注射选择性AT(1)受体拮抗剂坎地沙坦(500 pmol),可分别使升压和心动过速应激反应减弱31%和33%。坎地沙坦未改变进食行为或对进食的循环反应。这些结果表明,除了在介导应激反应中的作用外,DMH在调节与进食相关的心血管唤醒中可能也很重要。局部谷氨酸能输入似乎调节对应激和进食的心血管反应。相反,通过AT1受体起作用的血管紧张素II可能在DMH中选择性调节对应激的心血管反应,但不调节对进食的反应。