Jesmin Subrina, Sakuma Ichiro, Togashi Hiroko, Yoshioka Mitsuhiro, Hattori Yuichi, Kitabatake Akira, Miyauchi Takashi
Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
J Cardiovasc Pharmacol. 2004 Nov;44 Suppl 1:S59-63. doi: 10.1097/01.fjc.0000166223.57970.5f.
It is already well known that alteration of angiotensin II (Ang II) receptors results in cardiac remodeling in different pathological states, and it is believed that Ang II stimulates the release of endothelin-1 (ET-1). The present study aimed at investigating the interaction between ET-1 and different Ang II receptors in the heart of stroke-prone spontaneously hypertensive rats (SHR-SP). These were treated for 3 months with SB209670, an endothelin-A/endothelin-B dual receptor antagonist, or saline (vehicle) starting from the prehypertensive stage (6 weeks of age). Blood pressure, body weight, heart weight and left ventricular weight were sufficiently decreased after treatment of SHR-SP with SB209670. Ang II type 1 receptor was significantly upregulated in the heart of vehicle-treated SHR-SP compared with the age-matched control, Wistar-Kyoto rat. After endothelin antagonism with SB209670, Ang II type 1 receptor in SHR-SP heart was markedly suppressed. On the other hand, Ang II type 2 receptor was approximately 45% downregulated in the heart of vehicle-treated SHR-SP compared with that of the control, and recovered after endothelin antagonism. The present study demonstrates for the first time the effects of endothelin antagonism on the differential expression and regulation of Ang II receptors in the malignant hypertensive model, SHR-SP, and suggests that the endothelin system may be able to function on the upstream of Ang II signaling.
众所周知，血管紧张素II（Ang II）受体的改变会在不同病理状态下导致心脏重塑，并且人们认为Ang II会刺激内皮素-1（ET-1）的释放。本研究旨在探讨易卒中型自发性高血压大鼠（SHR-SP）心脏中ET-1与不同Ang II受体之间的相互作用。从高血压前期阶段（6周龄）开始，用内皮素-A/内皮素-B双受体拮抗剂SB209670或生理盐水（载体）对这些大鼠进行3个月的治疗。用SB209670治疗SHR-SP后，血压、体重、心脏重量和左心室重量均显著降低。与年龄匹配的对照Wistar-Kyoto大鼠相比，载体处理的SHR-SP心脏中1型Ang II受体显著上调。在用SB209670拮抗内皮素后，SHR-SP心脏中的1型Ang II受体明显受到抑制。另一方面，与对照组相比，载体处理的SHR-SP心脏中2型Ang II受体下调约45%，内皮素拮抗后恢复。本研究首次证明了内皮素拮抗对恶性高血压模型SHR-SP中Ang II受体差异表达和调节的影响，并表明内皮素系统可能在Ang II信号传导的上游发挥作用。
