Renal Division, Department of Medicine.
Department of Physiology, Emory University, Atlanta.
J Hypertens. 2018 Mar;36(3):510-519. doi: 10.1097/HJH.0000000000001596.
Protein kinase Cα (PKCα) is a critical regulator of multiple cell signaling pathways including gene transcription, posttranslation modifications and activation/inhibition of many signaling kinases. In regards to the control of blood pressure, PKCα causes increased vascular smooth muscle contractility, while reducing cardiac contractility. In addition, PKCα has been shown to modulate nephron ion transport. However, the role of PKCα in modulating mean arterial pressure (MAP) has not been investigated. In this study, we used a whole animal PKCα knock out (PKC KO) to test the hypothesis that global PKCα deficiency would reduce MAP, by a reduction in vascular contractility.
Radiotelemetry measurements of ambulatory blood pressure (day/night) were obtained for 18 h/day during both normal chow and high-salt (4%) diet feedings. PKCα mice had a reduced MAP, as compared with control, which was not normalized with high-salt diet (14 days). Metabolic cage studies were performed to determine urinary sodium excretion.
PKC KO mice had a significantly lower diastolic, systolic and MAP as compared with control. No significant differences in urinary sodium excretion were observed between the PKC KO and control mice, whether fed normal chow or high-salt diet. Western blot analysis showed a compensatory increase in renal sodium chloride cotransporter expression. Both aorta and mesenteric vessels were removed for vascular reactivity studies. Aorta and mesenteric arteries from PKC KO mice had a reduced receptor-independent relaxation response, as compared with vessels from control. Vessels from PKC KO mice exhibited a decrease in maximal contraction, compared with controls.
Together, these data suggest that global deletion of PKCα results in reduced MAP due to decreased vascular contractility.
蛋白激酶 Cα（PKCα）是包括基因转录、翻译后修饰以及许多信号激酶的激活/抑制在内的多种细胞信号通路的关键调节因子。就血压控制而言，PKCα 导致血管平滑肌收缩力增加，同时降低心肌收缩力。此外，PKCα 已被证明可调节肾单位离子转运。然而，PKCα 调节平均动脉压（MAP）的作用尚未得到研究。在这项研究中，我们使用全动物 PKCα 敲除（PKC KO）来测试以下假设：即由于血管收缩性降低，全局 PKCα 缺乏会降低 MAP。
在正常饮食和高盐（4%）饮食喂养期间，通过遥测法测量 18 小时/天的日间和夜间活动血压。与对照相比，PKCα 小鼠的 MAP 降低，而高盐饮食（14 天）并未使其正常化。进行代谢笼研究以确定尿钠排泄量。
与对照相比，PKC KO 小鼠的舒张压、收缩压和 MAP 明显降低。无论是正常饮食还是高盐饮食，PKC KO 和对照小鼠的尿钠排泄量均无显著差异。Western blot 分析显示肾钠氯协同转运蛋白表达代偿性增加。为了进行血管反应性研究，取出主动脉和肠系膜血管。与对照血管相比，PKC KO 小鼠的主动脉和肠系膜动脉的受体非依赖性松弛反应明显减弱。与对照相比，PKC KO 小鼠的血管最大收缩力降低。
综上所述，这些数据表明，由于血管收缩性降低，全局 PKCα 缺失导致 MAP 降低。
