Nitric oxide increases the activity of the apical 70 ps k+ channel
in the tal of rat kidney.
Lu, Ming, Xiaohong Wang, and Wenhui Wang.
Department of Pharmacology, New York Medical College. Valhalla, NY
10595
APStracts 5:0035F, 1998.
We have previously shown that nitric oxide (NO) mediates the
stimulatory effect of angiotensin II on the apical 70 pS K+ channel
in the thick ascending limb (TAL) of Henle's loop of the rat kidney
(12). In the present study, we used the patch-clamp technique to
examine the effects of NO on the 70 pS K+ channel. Addition of 10
[mu]M S-nitroso-N-acetyl-penicillamine (SNAP), an NO donor, increased
the channel activity in cell-attached patches. In contrast,
application of 100 [mu]M L-NAME (Nw-nitro-L-arginine methyl ester),
an inhibitor of nitric oxide synthase (NOS), reduced the channel
activity by 75+/-7%. The effect of L-NAME was the result of
inhibiting NOS, since D-NAME, which does not block NOS activity, had
no effect on the channel activity. In addition, the effect of L-NAME
was abolished in the presence of 1 mM L-arginine or by addition of 10
[mu]M SNAP, further supporting the role of NO. Finally, the L-NAME
-induced inhibition was also reversed by adding 8-Br-cGMP. That the
effect of NO is mediated by the cGMP-dependent pathway is also
suggested by experiments in which inhibition of guanylate cyclase
abolished the effect of SNAP. Finally, 10 [mu]M SNAP significantly
increased cGMP concentration of the medullary TAL from 12.4 fM/[mu]g
protein to 38.9 fM/[mu]g protein measured with ELISA. We conclude
that NO is involved in regulating the activity of the apical 70 pS K+
channel in the TAL of the rat kidney.
Received 3 September 1997; accepted in final form 5 February
1998.
APS Manuscript Number F281-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 19 February 1998