School of Physiology & Pharmacology, Bristol Heart Institute, Medical Science Building, University of Bristol, Bristol BS8 1TD, UK.
J Physiol. 2012 Sep 1;590(17):4269-77. doi: 10.1113/jphysiol.2012.237800. Epub 2012 Jun 11.
The peripheral chemoreflex is known to be enhanced in individuals with hypertension. In pre-hypertensive (PH) and adult spontaneously hypertensive rats (SHRs) carotid body type I (glomus) cells exhibit hypersensitivity to chemosensory stimuli and elevated sympathoexcitatory responses to peripheral chemoreceptor stimulation. Herein, we eliminated carotid body inputs in both PH-SHRs and SHRs to test the hypothesis that heightened peripheral chemoreceptor activity contributes to both the development and maintenance of hypertension. The carotid sinus nerves were surgically denervated under general anaesthesia in 4- and 12-week-old SHRs. Control groups comprised sham-operated SHRs and aged-matched sham-operated and carotid sinus nerve denervated Wistar rats. Arterial blood pressure was recorded chronically in conscious, freely moving animals. Successful carotid sinus nerve denervation (CSD) was confirmed by testing respiratory responses to hypoxia (10% O(2)) or cardiovascular responses to i.v. injection of sodium cyanide. In the SHR, CSD reduced both the development of hypertension and its maintenance (P<0.05) and was associated with a reduction in sympathetic vasomotor tone (as revealed by frequency domain analysis and reduced arterial pressure responses to administration of hexamethonium; P<0.05 vs. sham-operated SHR) and an improvement in baroreflex sensitivity. No effect on blood pressure was observed in sham-operated SHRs or Wistar rats. In conclusion, carotid sinus nerve inputs from the carotid body are, in part, responsible for elevated sympathetic tone and critical for the genesis of hypertension in the developing SHR and its maintenance in later life.
外周化学感受器反射在高血压患者中增强。在前期高血压(PH)和成年自发性高血压大鼠(SHR)中,颈动脉体 I 型(球)细胞对化学感觉刺激表现出超敏性,对外周化学感受器刺激的交感神经兴奋反应升高。在此,我们消除了 PH-SHR 和 SHR 中的颈动脉体输入,以测试外周化学感受器活性升高有助于高血压的发展和维持的假设。在全身麻醉下,通过手术对 4 周和 12 周龄 SHR 的颈动脉窦神经进行了神经切断。对照组包括假手术 SHR 以及年龄匹配的假手术和颈动脉窦神经切断的 Wistar 大鼠。在清醒、自由活动的动物中,通过记录动脉血压来进行慢性记录。通过测试对缺氧(10% O(2))或静脉注射氰化钠的心血管反应来成功进行颈动脉窦神经切断(CSD)。在 SHR 中,CSD 降低了高血压的发展和维持(P<0.05),并与交感血管运动张力降低(通过频域分析和对六烃季铵给药的动脉血压反应减少来揭示;P<0.05 与假手术 SHR 相比)和压力反射敏感性改善相关。假手术 SHR 或 Wistar 大鼠的血压无变化。总之,颈动脉体的颈动脉窦神经输入部分负责升高的交感神经张力,对于发展中的 SHR 的高血压发生及其后期生活中的维持至关重要。