Dietary intake of the heavy metal cadmium (Cd²⁺) is implicated in hypertension, but potassium supplementation reportedly mitigates hypertension. This study aims to elucidate the hypertensive mechanism of Cd²⁺. Vascular reactivity and protein expression were assessed in Cd²⁺-exposed rats for 8 weeks to determine the calcium-handling effect of Cd²⁺ and the possible signaling pathways and mechanisms involved. Cd²⁺ induced hypertension in vivo by significantly (p < 0.001) elevating systolic blood pressure (160 ± 2 and 155 ± 1 vs 120 ± 1 mm Hg), diastolic blood pressure (119 ± 2 and 110 ± 1 vs 81 ± 1 mm Hg), and mean arterial pressure (133 ± 2 and 125 ± 1 vs 94 ± 1 mm Hg) (SBP, DBP, and MAP, respectively), while potassium supplementation protected against elevation of these parameters. The mechanism involved augmentation of the phosphorylation of renal myosin light chain phosphatase targeting subunit 1 (MYPT1) at threonine 697 (T697) (2.58 ± 0.36 vs 1 ± 0) and the expression of p44 mitogen-activated protein kinase (MAPK) (1.78 ± 0.20 vs 1 ± 0). While acetylcholine (ACh)-induced relaxation was unaffected, 5 mg/kg b.w. Cd²⁺ significantly (p < 0.001) attenuated phenylephrine (Phe)-induced contraction of the aorta, and 2.5 mg/kg b.w. Cd²⁺ significantly (p < 0.05) augmented sodium nitroprusside (SNP)-induced relaxation of the aorta. These results support the vital role of the kidney in regulating blood pressure changes after Cd²⁺ exposure, which may be a key drug target for hypertension management. Given the differential response to Cd²⁺, it is apparent that its hypertensive effects could be mediated by myosin light chain phosphatase (MLCP) inhibition via phosphorylation of renal MYPT1-T697 and p44 MAPK. Further investigation of small arteries and the Rho-kinase/MYPT1 interaction is recommended.

饮食中摄入的重金属镉 (Cd ²⁺ ) 与高血压有关，但据报道补充钾可减轻高血压。本研究旨在阐明Cd ²⁺的高血压机制。^{在暴露于 Cd 2+}的大鼠中评估血管反应性和蛋白质表达8 周，以确定 Cd ²⁺的钙处理作用以及可能涉及的信号通路和机制。Cd ²⁺诱发的体内高血压显着 ( p < 0.001) 升高收缩压（160 ± 2 和 155 ± 1 vs 120 ± 1 mm Hg）、舒张压（119 ± 2 和 110 ± 1 vs 81 ± 1 mm Hg）和平均动脉压（133 ± 2和 125 ± 1 vs 94 ± 1 mm Hg)（分别为 SBP、DBP 和 MAP），而补钾可防止这些参数升高。该机制涉及肾肌球蛋白轻链磷酸酶靶向亚基 1 (MYPT1) 在苏氨酸 697 (T697) (2.58 ± 0.36 vs 1 ± 0) 的磷酸化和 p44 丝裂原活化蛋白激酶 (MAPK) 的表达 (1.78 ± 0.20 对 1 ± 0)。虽然乙酰胆碱 (ACh) 诱导的舒张不受影响，但 5 mg/kg bw Cd ²⁺显着 ( p  < 0.001) 减弱了去氧肾上腺素 (Phe) 诱导的主动脉收缩，而 2.5 mg/kg bw Cd²⁺显着 ( p  < 0.05) 增强了硝普钠 (SNP) 诱导的主动脉松弛。^{这些结果支持肾脏在 Cd 2+}暴露后调节血压变化中的重要作用，这可能是高血压管理的关键药物靶点。鉴于对 Cd ²⁺的不同反应，很明显其高血压作用可能是通过肾 MYPT1-T697 和 p44 MAPK 的磷酸化抑制肌球蛋白轻链磷酸酶 (MLCP) 来介导的。建议进一步研究小动脉和 Rho 激酶/MYPT1 相互作用。