Nishikimi Toshio, Wang Xin, Akimoto Kazumi, Tadokoro Kazuyoshi, Mori Yosuke, Ishikawa Yayoi, Ishimura Kimihiko, Yoshihara Fumiki, Minamino Naoto, Kangawa Kenji, Matsuoka Hiroaki
Department of Hypertension and Cardiorenal Medicine, Dokkyo University School of Medicine, Mibu, Tochigi 321-0293, Japan.
Regul Pept. 2005 Jan 15;124(1-3):89-98. doi: 10.1016/j.regpep.2004.07.003.
We investigated the pathophysiological role of the renal adrenomedullin (AM) system, including the ligand, receptor, and amidating activity, in severe hypertensive rats.
We studied three groups: control Wistar Kyoto rats (WKY), spontaneously hypertensive stroke-prone rats (SHR-SP), and diuretic-treated SHR-SP. We measured AM-mature, active form, and AM-total (active form+inactive form) in plasma and renal tissues, and mRNA levels of AM and AM receptor system components such as calcitonin receptor-like receptor (CRLR), receptor activity-modifying protein (RAMP) 2, and RAMP3 in renal tissues.
SHR-SP had higher blood pressure, plasma neurohumoral factors, and lower renal function than WKY. SHR-SP had higher AM-mature and AM-total levels in plasma and renal tissues than WKY. Although the plasma AM-mature/AM-total ratio was similar in the two groups, AM-mature/AM-total ratio in renal tissues was higher in SHR-SP than in WKY. In addition, mRNA levels of AM in the renal cortex and medulla and the mRNA levels of CRLR, RAMP2, and RAMP3 in the renal cortex were higher in SHR-SP than in WKY. Chronic diuretic treatment decreased blood pressure and improved kidney function and neurohumoral factors, with reductions in plasma and renal AM system.
Upregulation of circulating and renal AM system may modulate pathophysiology in SHR-SP.
我们研究了肾肾上腺髓质素（AM）系统，包括配体、受体和酰胺化活性，在重度高血压大鼠中的病理生理作用。
我们研究了三组：对照Wistar Kyoto大鼠（WKY）、自发性高血压易卒中大鼠（SHR-SP）和接受利尿剂治疗的SHR-SP。我们测量了血浆和肾组织中AM成熟、活性形式以及AM总量（活性形式+非活性形式），以及肾组织中AM和AM受体系统组分如降钙素受体样受体（CRLR）、受体活性修饰蛋白（RAMP）2和RAMP3的mRNA水平。
与WKY相比，SHR-SP具有更高的血压、血浆神经体液因子以及更低的肾功能。与WKY相比，SHR-SP血浆和肾组织中的AM成熟和AM总量水平更高。尽管两组血浆中AM成熟/AM总量的比值相似，但SHR-SP肾组织中的AM成熟/AM总量比值高于WKY。此外，SHR-SP肾皮质和髓质中AM的mRNA水平以及肾皮质中CRLR、RAMP2和RAMP3的mRNA水平均高于WKY。慢性利尿剂治疗可降低血压、改善肾功能和神经体液因子，并降低血浆和肾AM系统水平。
循环和肾AM系统的上调可能调节SHR-SP的病理生理过程。
