Angiotensin II stimulates basolateral K channels in rat cortical collecting ducts.
We used the patch-clamp technique to study the effects of angiotensin II (ANG II) on basolateral K channels in cortical collecting ducts (CCDs). Application of ANG II (100 pM-100 nM) increased the activity of basolateral 18-pS K channels. This effect of ANG II was completely abolished by losartan, which is an antagonist of type 1 angiotensin (AT(1)) receptors. In contrast, inhibition of type 2 angiotensin (AT(2)) receptors did not block the stimulatory effect of ANG II. Also, application of ANG II significantly increased intracellular Ca(2+) concentrations, which were measured with fura 2 dye. To explore the role of Ca(2+)-dependent pathways in the regulation of basolateral K channels, the effects of ANG II on channel activity were examined in the presence of arachidonyltrifluoromethyl ketone to inhibit phospholipase A(2) (PLA(2)), GF-109203X [a protein kinase C (PKC) inhibitor], and N(G)-nitro-l-arginine methyl ester (l-NAME) to inhibit nitric oxide synthase. Inhibition of either PLA(2) or PKC did not block the effect of ANG II on basolateral K-channel activity. However, the stimulatory effect of ANG II was absent in the CCDs treated with l-NAME. Moreover, addition of the membrane-permeant 8-bromo-guanosine 3',5'-cyclic monophosphate (8-bromo-cGMP) not only increased channel activity but also abolished the stimulatory effect of ANG II on channel activity. We conclude that ANG II increases basolateral K-channel activity via the stimulation of AT(1) receptors, and the stimulatory effect of ANG II is mediated by a nitric oxide-dependent cGMP pathway.
Wei
Yuan
Y
Department of Pharmacology, New York Medical College, Valhalla 10595, USA.
Wang
Wenhui
W
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007672:Kidney Cortex / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D015221:Potassium Channels; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D006152:Cyclic GMP; D011188:Potassium; D019331:NG-Nitroarginine Methyl Ester