Department of Physiology and Functional Genomics and McKnight Brain Institute, College of Medicine, University of Florida, 1600 Southwest Archer Road, PO-BOX: 100274, Gainesville, FL 32610, USA.
Cardiovasc Res. 2013 Jan 1;97(1):153-60. doi: 10.1093/cvr/cvs297. Epub 2012 Sep 20.
The macrophage migration inhibitory factor (MIF) is an intracellular inhibitor of the central nervous system actions of angiotensin II on blood pressure. Considering that angiotensin II actions at the nucleus of the solitary tract are important for the maintenance of hypertension in spontaneously hypertensive rats (SHRs), we tested if increased MIF expression in the nucleus of the solitary tract of SHR alters the baseline high blood pressure in these rats.
Eight-week-old SHRs or normotensive rats were microinjected with the vector AAV2-CBA-MIF into the nucleus of the solitary tract, resulting in MIF expression predominantly in neurons. Rats also underwent recordings of the mean arterial blood pressure (MAP) and heart rate (via telemetry devices implanted in the abdominal aorta), cardiac- and baroreflex function. Injections of AAV2-CBA-MIF into the nucleus of the solitary tract of SHRs produced significant decreases in the MAP, ranging from 10 to 20 mmHg, compared with age-matched SHRs that had received identical microinjections of the control vector AAV2-CBA-eGFP. This lowered MAP in SHRs was maintained through the end of the experiment at 31 days, and was associated with an improvement in baroreflex function to values observed in normotensive rats. In contrast to SHRs, similar increased MIF expression in the nucleus of the solitary tract of normotensive rats produced no changes in baseline MAP and baroreflex function.
These results indicate that an increased expression of MIF within the nucleus of the solitary tract neurons of SHRs lowers blood pressure and restores baroreflex function.
巨噬细胞移动抑制因子（MIF）是一种细胞内抑制剂，可抑制血管紧张素 II 在中枢神经系统对血压的作用。鉴于血管紧张素 II 在孤束核的作用对于维持自发性高血压大鼠（SHR）的高血压很重要，我们测试了 SHR 孤束核中 MIF 表达增加是否会改变这些大鼠的基础高血压。
8 周龄的 SHR 或正常血压大鼠被微注射 AAV2-CBA-MIF 进入孤束核，导致 MIF 主要在神经元中表达。大鼠还进行了平均动脉血压（MAP）和心率（通过植入腹主动脉的遥测设备）、心脏和压力反射功能的记录。将 AAV2-CBA-MIF 注射到 SHR 的孤束核中，与接受相同对照载体 AAV2-CBA-eGFP 微注射的年龄匹配的 SHR 相比，MAP 显著降低 10-20mmHg。这种 SHR 的 MAP 降低在 31 天的实验结束时得以维持，并且与在正常血压大鼠中观察到的压力反射功能改善相关。与 SHR 不同，正常血压大鼠孤束核中 MIF 表达的类似增加并未导致基线 MAP 和压力反射功能发生变化。
这些结果表明，SHR 孤束核神经元中 MIF 的表达增加可降低血压并恢复压力反射功能。
