| Autor: |
HeIle, Frank, Hultström, Michael, Skogstrand, Trude, Palm, Fredrik, Iversen, Bjarne M. |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Renal Physiology; Jan2009, Vol. 296, pF78-F86, 9p, 2 Black and White Photographs, 17 Graphs |
| Abstrakt: |
Two-kidney, one-clip (2K1C) is a model of renovascular hypertension where we previously found an exaggerated intracellular calcium (Ca-12+) response to ANG II in isolated afferent arterioles (AAs) from the clipped kidney (Helle F, Vagnes OB, Iversen BM. Am J Physiol Renal Physiol 291: F 140- F147, 2006). To test whether nitric oxide (NO) ameliorates the exaggerated ANG II response in 2K1C, we studied ANG II (l0-7 mol/1)-induced calcium signaling and contractility with or without the NO synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME). In AAs from the nonclipped kidney, L-NAME increased the ANG IT-induced Cai2+ response from 0.28 ± 0.05 to 0.55 ± 0.09 (fura 2, 340 nm/380 nm ratio) and increased contraction from 80 ± 6 to 60 ± 6% of baseline (P < 0.05). In vessels from sham and clipped kidneys, L-NAME had no effect. In diaminofluorescein-FM diacetate-loaded AAs from the nonclipped kidney, ANG II increased NO-derived fluorescence to 145 ± 34% of baseline (P < 0.05 vs. sham), but not in vessels from the sham or clipped kidney. Endothelial NOS (eNOS) mRNA and ser-l 177 phosphorylation were unchanged in both kidneys from 2K1C, while eNOS protein was reduced in the clipped kidney compared with sham. cationic amino acid transferase-1 and 2 mRNAs were increased in 2K1C, indicating increased availability of L-arginine for NO synthesis, but counteracted by decreased scavenging of the eNOS inhibitor asymmetric dimethyl-arginine by dimethylarginine dimethylaminohydrolase 2. In conclusion, the Cai2+ and contractile responses to ANG II are blunted by NO release in the nonclipped kidney. This may protect the nonclipped kidney from the hypertension and elevated ANG II levels in 2K1C. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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