NO/cGMP signaling modulates regulation of Na+-K+-ATPase activity by angiotensin II in rat proximal tubules.
ANG II exerts a biphasic effect on Na+ transport in the kidney through its effects on Na+-K+-ATPase activity. Beginning at 10(-13) M, ANG II increased Na+-K+-ATPase in freshly isolated rat proximal tubules to a maximum stimulation at 10(-11) M of 1.43 +/- 0.08-fold above control. Stimulation decreased progressively at concentrations >10(-10) M to a value of 0.96 +/- 0.1-fold at 10(-7) M. In the presence of additional L-arginine, the substrate for NO synthesis, the stimulatory effect of ANG II (10(-11) M) was lost. Conversely, N-monomethyl-L-arginine (L-NMMA), the nitric oxide (NO) synthase inhibitor, unmasked the stimulatory effect of ANG II at 10(-7) M (1.40 +/- 0.1-fold). 1H-[1,2,4]oxadiazole-[4,3-a]quinoxalin-1-one, the soluble guanylyl cyclase inhibitor, like L-NMMA, unmasked the stimulatory effect of ANG II at 10(-7) M (1.30 +/- 0.1-fold). The intracellular cGMP concentration was increased 1.58 +/- 0.28-fold at 10(-7) M ANG II. The ANG II AT(1) receptor antagonist SK&F 108566 blocked the stimulatory effect of ANG II at 10(-11) M. These data suggest that the NO/cGMP signaling pathway serves as a negative component in the regulation of Na+-K+-ATPase activity by ANG II.
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Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, 4301 West Markham St. slot 611, Little Rock, AR 72205, USA.
Mayeux
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D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D006152:Cyclic GMP / Q000096:biosynthesis / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D007425:Intracellular Membranes / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D010069:Oxadiazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D015398:Signal Transduction / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D012995:Solubility; D019323:omega-N-Methylarginine / Q000494:pharmacology
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D057911:Angiotensin Receptor Antagonists; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D011810:Quinoxalines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D006162:Guanylate Cyclase; D000254:Sodium-Potassium-Exchanging ATPase; D006152:Cyclic GMP; D002118:Calcium