Angiotensin II signaling activities the NO-cGMP pathway in rat proximal tubules.
Angiotensin II signaling activities the NO-cGMP pathway in rat proximal tubules.
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DOI：
10.1016/s0024-3205(98)00278-1
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发表时间：
1998-06
期刊：
影响因子：
6.1
通讯作者：
C. Zhang;P. Mayeux
中科院分区：
文献类型：
--
作者：
C. Zhang;P. Mayeux
We examined the signal transduction cascade of angiotensin II in isolated rat proximal tubules. Angiotensin II induced a rapid (15 sec) concentration-dependent rise in intracellular free Ca2+(EC50= 1.7 nM). The rise in Ca2+was blocked by the angiotensin II receptor AT1specific antagonist SK&F 108566. This indicates that the rise in Ca2+is fully mediated by AT1receptors. To characterize further the antagonism by SK&F 108566, the Schild analysis was performed (pA2= 10.9 ± 0.14 and slope = 0.94 ± 0.11; n = 3). It indicated that SK&F 108566 is a high affinity competitive antagonist at AT1receptors in the proximal tubule. Angiotensin II signaling also induced a rapid (5 min) rise in cGMP formation. This response was blocked by SK&F 108566, by inhibition of nitric oxide synthase, or by inhibition of soluble guanylyl cyclase. This indicates that the formation of cGMP elicited by angiotensin II is mediated by AT1receptors and activation of the NO-cGMP pathway. Since cGMP can inhibit Na, K-ATPase activity, activation of the NO-cGMP pathway may act as a negative feedback component of angiotensin II signaling in renal proximal tubules.
