Geriatric Research, Education, and Clinical Center, Veterans Affairs Medical Center, Salt Lake City, Utah.
Department of Internal Medicine, University of Utah, Salt Lake City, Utah.
Am J Physiol Regul Integr Comp Physiol. 2022 Aug 1;323(2):R221-R226. doi: 10.1152/ajpregu.00007.2022. Epub 2022 May 24.
The exercise pressor reflex (EPR), a neurocirculatory control mechanism, is exaggerated in hypertensive humans and rats. Disease-related abnormalities within the afferent arm of the reflex loop, including mechano- and metabosensitive receptors located at the terminal end of group III/IV muscle afferents, may contribute to the dysfunctional EPR in hypertension. Using control (WKY) and spontaneous hypertensive (SHR) rats, we examined dorsal root ganglion (DRG) gene and protein expression of molecular receptors recognized as significant determinants of the EPR. Twelve lumbar DRGs (6 left, 6 right) were harvested from each of 10 WKY [arterial blood pressure (MAP): 96 ± 9 mmHg] and 10 SHR (MAP: 144 ± 9 mmHg). DRGs from the left side were used for protein expression (Western blotting; normalized to GAPDH), whereas right-side DRGs (i.e., parallel structure) were used to determine mRNA levels (RNA-sequencing, normalized to TPM). Analyses focused on metabosensitive (ASIC3, Bradykinin receptor B2, EP4, P2X3, TRPv1) and mechanosensitive (Piezo1/2) receptors. Although Piezo1 was similar in both groups ( = 0.75), protein expression for all other receptors was significantly higher in SHR compared with WKY. With the exception of a greater Bradykinin-receptor B2 in SHR ( < 0.05), mRNA expression of all other receptors was not different between groups ( > 0.18). The higher protein content of these sensory receptors in SHR indirectly supports the previously proposed hypothesis that the exaggerated EPR in hypertension is, in part, due to disease-related abnormalities within the afferent arm of the reflex loop. The upregulated receptor content, combined with normal mRNA levels, insinuates that posttranscriptional regulation of sensory receptor protein expression might be impaired in hypertension.
运动升压反射（EPR）是一种神经循环控制机制，在高血压患者和大鼠中被夸大。反射环路传入臂中的与疾病相关的异常，包括位于 III/IV 类肌传入末端的机械和代谢敏感受体，可能导致高血压中 EPR 的功能障碍。我们使用对照（WKY）和自发性高血压（SHR）大鼠，检查了被认为是 EPR 重要决定因素的分子受体的背根神经节（DRG）基因和蛋白表达。从每组 10 只 WKY（MAP：96 ± 9mmHg）和 10 只 SHR（MAP：144 ± 9mmHg）中收获 12 个腰椎 DRG（左侧 6 个，右侧 6 个）。左侧 DRG 用于蛋白表达（Western 印迹；用 GAPDH 归一化），而右侧 DRG（即平行结构）用于确定 mRNA 水平（RNA 测序，用 TPM 归一化）。分析集中在代谢敏感（ASIC3、缓激肽受体 B2、EP4、P2X3、TRPv1）和机械敏感（Piezo1/2）受体上。虽然 Piezo1 在两组之间相似（ = 0.75），但所有其他受体的蛋白表达在 SHR 中均显著高于 WKY。除了 SHR 中缓激肽受体 B2 更高（ < 0.05）之外，所有其他受体的 mRNA 表达在两组之间没有差异（ > 0.18）。这些感觉受体在 SHR 中的蛋白含量更高，间接支持了之前提出的假说，即高血压中 EPR 的夸大部分是由于反射环路传入臂中的与疾病相关的异常。上调的受体含量，加上正常的 mRNA 水平，暗示高血压中感觉受体蛋白表达的转录后调节可能受损。
