Ingert Catherine, Grima Michèle, Coquard Catherine, Barthelmebs Mariette, Imbs Jean-Louis
Institut de Pharmacologie, Faculté de Médecine, Université Louis Pasteur, 67085 Strasbourg France.
Am J Physiol Renal Physiol. 2002 Nov;283(5):F1003-10. doi: 10.1152/ajprenal.00322.2001.
This study was designed to determine the involvement of AT(1) receptors in the uptake of ANG II in the kidney of rats exposed to differing salt intake. Male Wistar-Kyoto rats were treated with a normal-salt (NS; 1% NaCl, n = 7) or a low-salt (LS; 0.025% NaCl, n = 7) diet combined with (LS+Los, n = 7; NS+Los, n = 7) or without losartan (30 mg. kg(-1). day(-1)), an AT(1) receptor antagonist. Renin (RA) and angiotensin-converting enzyme (ACE) activities and angiotensinogen, ANG I, and ANG II levels were measured in plasma, renal cortex, and medulla. In LS rats, in both plasma and renal cortex, the increase in RA was associated with an increase in ANG I and ANG II levels compared with NS rats, but intrarenal ANG II levels increased more than ANG I levels. In NS+Los rats, the increase in RA in plasma was followed by a marked increase in plasma ANG I and ANG II levels compared with NS rats whereas in the kidney the increase of renal RA was followed by a decrease of the levels of these peptides. The same pattern was observed in LS+Los rats, but the decrease in renal ANG II levels was much more pronounced in LS+Los rats than in NS+Los rats. Our results suggest that the increase in renal ANG II levels after salt restriction results mainly from an uptake of ANG II, via AT(1) receptors. Such elevated intrarenal ANG II levels could contribute to maintain sodium and fluid balance and arterial blood pressure during salt-deficiency states.
本研究旨在确定1型血管紧张素（AT(1)）受体在不同盐摄入量的大鼠肾脏中对血管紧张素II（ANG II）摄取的参与情况。雄性Wistar-Kyoto大鼠接受正常盐（NS；1%氯化钠，n = 7）或低盐（LS；0.025%氯化钠，n = 7）饮食，并联合（LS+氯沙坦，n = 7；NS+氯沙坦，n = 7）或不联合氯沙坦（30毫克·千克⁻¹·天⁻¹），氯沙坦为一种AT(1)受体拮抗剂。测定血浆、肾皮质和髓质中的肾素（RA）和血管紧张素转换酶（ACE）活性以及血管紧张素原、ANG I和ANG II水平。在LS大鼠中，与NS大鼠相比，血浆和肾皮质中RA的增加与ANG I和ANG II水平的增加相关，但肾内ANG II水平的增加超过ANG I水平。在NS+氯沙坦大鼠中，与NS大鼠相比，血浆中RA的增加之后是血浆ANG I和ANG II水平的显著增加，而在肾脏中，肾RA的增加之后是这些肽水平的降低。在LS+氯沙坦大鼠中观察到相同的模式，但LS+氯沙坦大鼠中肾ANG II水平的降低比NS+氯沙坦大鼠中更明显。我们的结果表明，限盐后肾内ANG II水平的增加主要源于通过AT(1)受体对ANG II的摄取。这种升高的肾内ANG II水平可能有助于在缺盐状态下维持钠和液体平衡以及动脉血压。
