Sphingolipids exert important roles within the cardiovascular system and related diseases. Perturbed sphingolipid metabolism was previously reported in cerebral and renal tissues of spontaneously hypertensive rats (SHR). Specific defects related to the synthesis of sphingolipids and to the metabolism of Sphingosine-1-Phospahte (S1P) were exclusively identified in the stroke-prone (SHRSP) with the respect to the stroke-resistant (SHRSR) strain.

In this study, we explored any existing perturbation in either protein or gene expression of enzymes involved in the sphingolipid pathways in cardiac tissue from both SHRSP and SHRSR strains, compared to the normotensive Wistar Kyoto (WKY) strain.

The two hypertensive rat models showed an overall perturbation of the expression of different enzymes involved in the sphingolipid metabolism in the heart. In particular, whereas the expression of the S1P-metabolizing-enzyme, SPHK2, was significantly reduced in both SHR strains, SGPL1 protein levels were decreased only in SHRSP. The protein levels of S1P receptors 1–3 were reduced only in the cardiac tissue of SHRSP, whereas S1PR2 levels were reduced in both SHR strains. The de novo synthesis of sphingolipids was aberrant in the two hypertensive strains. A significant reduction of mRNA expression of the Sgms1 and Smpd3 enzymes, implicated in the metabolism of sphingomyelin, was found in both hypertensive strains. Interestingly, Smpd2, devoted to sphingomyelin degradation, was reduced only in the heart of SHRSP.

In conclusion, alterations in the expression of sphingolipid-metabolizing enzymes may be involved in the susceptibility to cardiac damage of hypertensive rat strains. Specific differences detected in the SHRSP, however, deserve further elucidation.

鞘脂在心血管系统和相关疾病中发挥重要作用。先前报道自发性高血压大鼠（SHR）的脑和肾组织中鞘脂代谢受到干扰。相对于中风抗性菌株（SHRSR），在易中风菌株（SHRSP）中专门发现了与鞘脂合成和 1-磷酸鞘氨醇（S1P）代谢相关的特定缺陷。

在这项研究中，我们探讨了与正常血压 Wistar京都 (WKY) 菌株相比，SHRSP 和 SHRSR 菌株心脏组织中参与鞘脂通路的酶的蛋白质或基因表达是否存在任何扰动。

两种高血压大鼠模型显示心脏中参与鞘脂代谢的不同酶的表达总体受到干扰。特别是，尽管 S1P 代谢酶 SPHK2 的表达在两种 SHR 菌株中均显着降低，但 SGPL1 蛋白水平仅在 SHRSP 中降低。S1P 受体 1-3的蛋白水平仅在 SHRSP 的心脏组织中降低，而 S1PR2 水平在两种 SHR 品系中均降低。两种高血压菌株中鞘脂的从头合成是异常的。在两种高血压菌株中均发现与鞘磷脂代谢有关的Sgms1和Smpd3酶的 mRNA 表达显着降低有趣的是，负责鞘磷脂降解的Smpd2仅在 SHRSP 的核心部位减少。

总之，鞘脂代谢酶表达的改变可能与高血压大鼠品系心脏损伤的易感性有关。然而，SHRSP 中发现的具体差异值得进一步阐明。