Matin Nusrat, Pires Paulo W, Garver Hannah, Jackson William F, Dorrance Anne M
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA.
Department of Pharmacology, Center for Cardiovascular Research, University of Nevada School of Medicine, Reno, NV, USA.
Microcirculation. 2016 Oct;23(7):571-579. doi: 10.1111/micc.12308.
Chronic hypertension induces detrimental changes in the structure and function of surface cerebral arteries. Very little is known about PAs, which perfuse distinct neuronal populations in the cortex and may play a role in cerebrovascular disorders. We investigated the effect of DOCA-salt induced hypertension on endothelial function and artery structure in PAs and MCAs.
Uninephrectomized male Sprague-Dawley rats were implanted with a subcutaneous pellet containing DOCA (150 mg/kg b.w.) and drank salt water (1% NaCl and 0.2% KCl) for 4 weeks. Sham rats were uninephrectomized and drank tap water. Vasoreactivity and passive structure in the MCAs and the PAs were assessed by pressure myography.
Both MCAs and PAs from DOCA-salt rats exhibited impaired endothelium-dependent dilation (P<.05). In the PAs, addition of NO and COX inhibitors enhanced dilation in DOCA-salt rats (P<.05), suggesting that dysfunctional NO and COX-dependent signaling could contribute to impaired endothelium-mediated dilation. MCAs from DOCA-salt rats exhibited inward remodeling (P<.05).
Hypertension-induced MCA remodeling coupled with impaired endothelium-dependent dilation in both the MCAs and PAs may exacerbate the risk of cerebrovascular accidents and the associated morbidity and mortality.
慢性高血压会导致大脑表面动脉的结构和功能发生有害变化。对于穿通动脉(PAs),人们了解甚少,它们为皮质中不同的神经元群体供血,可能在脑血管疾病中发挥作用。我们研究了去氧皮质酮盐(DOCA)诱导的高血压对穿通动脉和大脑中动脉(MCAs)内皮功能和动脉结构的影响。
对单侧肾切除的雄性Sprague-Dawley大鼠皮下植入含DOCA(150 mg/kg体重)的药丸,并饮用盐水(1% NaCl和0.2% KCl)4周。假手术大鼠进行单侧肾切除并饮用自来水。通过压力肌动描记法评估大脑中动脉和穿通动脉的血管反应性和被动结构。
DOCA-盐处理大鼠的大脑中动脉和穿通动脉均表现出内皮依赖性舒张功能受损(P<0.05)。在穿通动脉中,添加一氧化氮(NO)和环氧化酶(COX)抑制剂可增强DOCA-盐处理大鼠的舒张功能(P<0.05),这表明功能失调的NO和COX依赖性信号传导可能导致内皮介导的舒张功能受损。DOCA-盐处理大鼠的大脑中动脉表现出内向重塑(P<0.05)。
高血压诱导的大脑中动脉重塑,以及大脑中动脉和穿通动脉内皮依赖性舒张功能受损,可能会增加脑血管意外的风险以及相关的发病率和死亡率。