Hirose Takuo, Takahashi Kazuhiro, Mori Nobuyoshi, Nakayama Takashi, Kikuya Masahiro, Ohkubo Takayoshi, Kohzuki Masahiro, Totsune Kazuhito, Imai Yutaka
Department of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences and Medicine, Sendai, Japan.
Peptides. 2009 Jun;30(6):1124-9. doi: 10.1016/j.peptides.2009.02.009. Epub 2009 Feb 21.
Urotensin II (UII) and urotensin II-related peptide (URP) are novel vasoactive peptides that share urotensin II receptor (UT). We have recently reported that expressions of URP and UT were up-regulated in kidneys of rats with renal failure or hypertension. To clarify possible changes of the UII system expression in cardiovascular organs with hypertension, we examined the gene expression of UII, URP and UT in hearts and aortae of hypertensive rats. Furthermore, the expression was compared with that of endothelin-1 (ET-1). Quantitative reverse transcription polymerase chain reaction analysis showed that expression levels of UII mRNA and UT mRNA were significantly elevated in the atrium of 11-12-week-old spontaneously hypertensive rats (SHR) compared with age-matched Wistar-Kyoto rats (WKY). Moreover, UT mRNA expression was elevated in the ventricle of 11-12-week-old SHR. In the aorta, expression levels of URP mRNA and UT mRNA were significantly elevated in 11-12-week-old SHR compared with age-matched WKY, similarly to those in the kidney. In contrast, expression levels of ET-1 were significantly decreased in both the heart and the kidney of 11-12-week-old SHR compared with age-matched WKY. Immunohistochemistry showed that URP and UT were immunostained in cardiomyocytes, with weaker immunostaining in vascular endothelial and smooth muscle cells, in both SHR and WKY. These findings indicate that the gene expression of the UII system components (UII, URP and UT) and ET-1 is differently regulated in hypertension, and that the UII system in the heart and aortae may have certain pathophysiological roles in hypertension.
尾加压素 II(UII)和尾加压素 II 相关肽(URP)是一类新型的血管活性肽,它们共同作用于尾加压素 II 受体(UT)。我们最近报道,在肾衰竭或高血压大鼠的肾脏中,URP 和 UT 的表达上调。为了阐明高血压状态下心血管器官中 UII 系统表达的可能变化,我们检测了高血压大鼠心脏和主动脉中 UII、URP 和 UT 的基因表达。此外,还将其表达与内皮素 -1(ET-1)的表达进行了比较。定量逆转录聚合酶链反应分析表明,与年龄匹配的Wistar - Kyoto大鼠(WKY)相比,11 - 12周龄自发性高血压大鼠(SHR)心房中 UII mRNA 和 UT mRNA 的表达水平显著升高。此外,11 - 12周龄SHR的心室中 UT mRNA 表达也升高。在主动脉中,与年龄匹配的WKY相比,11 - 12周龄SHR中 URP mRNA 和 UT mRNA 的表达水平显著升高,与肾脏中的情况类似。相反,与年龄匹配的WKY相比,11 - 12周龄SHR心脏和肾脏中 ET-1 的表达水平均显著降低。免疫组织化学显示,在SHR和WKY中,URP和UT均在心肌细胞中被免疫染色,在血管内皮和平滑肌细胞中的免疫染色较弱。这些发现表明,UII系统成分(UII、URP和UT)和ET-1的基因表达在高血压中受到不同的调节,并且心脏和主动脉中的UII系统可能在高血压中具有一定的病理生理作用。