Shi S J, Rakugi H, Higashimori K, Jiang B B, Higaki J, Mikami H, Ogihara T
Department of Geriatric Medicine, Osaka University Medical School, Japan.
Biochem Biophys Res Commun. 1994 Jul 15;202(1):246-51. doi: 10.1006/bbrc.1994.1919.
We investigated the release of endothelin-1 (ET) from rat mesenteric arteries to clarify its pathophysiological role in the sustained hypertension of spontaneously hypertensive rats (SHR) following nephrectomy and the regulatory mechanism of the ET release which might be modified by vascular angiotensins and bradykinins. Nephrectomy increased the plasma level of ET and enhanced the ET release in both SHR and Wistar-Kyoto rats (WKY). CV-11974, an angiotensin II receptor antagonist, did not affect the ET release from arteries of nephrectomized rats. On the contrary, infusion of captopril, a converting enzyme inhibitor, further enhanced the ET release in both intact and nephrectomized rats. These findings suggest that the release of ET from mesenteric arteries may be regulated by bradykinins, but not by angiotensins. This pressor substance does not contribute to the sustained hypertension because the enhanced production of ET observed in both SHR and WKY. However, there is a possibility that the exaggerated responsiveness of vascular ET may in part account for local vascular tone and vascular remodeling in renal dysfunction.
我们研究了大鼠肠系膜动脉内皮素-1（ET）的释放，以阐明其在肾切除术后自发性高血压大鼠（SHR）持续性高血压中的病理生理作用，以及ET释放的调节机制，该机制可能会被血管血管紧张素和缓激肽所改变。肾切除术增加了ET的血浆水平，并增强了SHR和Wistar-Kyoto大鼠（WKY）的ET释放。血管紧张素II受体拮抗剂CV-11974对肾切除大鼠动脉的ET释放没有影响。相反，血管紧张素转换酶抑制剂卡托普利的输注进一步增强了完整大鼠和肾切除大鼠的ET释放。这些发现表明，肠系膜动脉ET的释放可能受缓激肽调节，而不受血管紧张素调节。这种升压物质对持续性高血压没有影响，因为在SHR和WKY中均观察到ET产生增加。然而，血管ET反应过度可能在一定程度上解释了肾功能不全时的局部血管张力和血管重塑。
