%0 Electronic Article %A Plato, Craig F. and Garvin, Jeffrey L. %I American Physiological Society %D 2001 %D 2001 %G English %@ 1931-857X %@ 1522-1466 %~ Katalog UB TU-Chemnitz %T α2-Adrenergic-mediated tubular NO production inhibits thick ascending limb chloride absorption %V 281 %J American Journal of Physiology-Renal Physiology %V 281 %N 4 %P F679-F686 %U http://dx.doi.org/10.1152/ajprenal.2001.281.4.f679 %X Stimulation of α2-adrenergic receptors inhibits transport in various nephron segments, and the thick ascending limb of the loop of Henle (THAL) expresses α2-receptors. We hypothesized that selective α2-receptor activation decreases NaCl absorption by cortical THALs through activation of NOS and increased production of NO. We found that the α2-receptor agonist clonidine (10 nM) decreased chloride flux ( JCl) from 119.5 ± 15.9 to 67.4 ± 13.8 pmol · mm−1· min−1(43% reduction; P < 0.02), whereas removal of clonidine from the bath increased JClby 20%. When NOS activity was inhibited by pretreatment with 5 mM NG-nitro-l-arginine methyl ester, the inhibitory effects of clonidine on THAL JClwere prevented (81.7 ± 10.8 vs. 71.6 ± 6.9 pmol · mm−1· min−1). Similarly, when the NOS substrate l-arginine was deleted from the bath, addition of clonidine did not decrease THAL JClfrom control (106.9 ± 11.6 vs. 132.2 ± 21.3 pmol · mm−1· min−1). When we blocked the α2-receptors with rauwolscine (1 μM), we found that the inhibitory effect of 10 nM clonidine on THAL JClwas abolished, verifying that α2, rather than I1, receptors mediate the effects of clonidine in the THAL. We investigated the mechanism of NOS activation and found that intracellular calcium concentration did not increase in response to clonidine, whereas pretreatment with 150 nM wortmannin abolished the clonidine-mediated inhibition of THAL JCl, indicating activation of phosphatidylinositol 3-kinase and the Akt pathway. We found that pretreatment of THALs with 10 μM LY-83583, an inhibitor of soluble guanylate cyclase, blocked clonidine-mediated inhibition of THAL JCl. In conclusion, α2-receptor stimulation decreases THAL JClby increasing NO release and stimulating guanylate cyclase. These data suggest that α2-receptors act as physiological regulators of THAL NO synthesis, thus inhibiting chloride transport and participating in the natriuretic and diuretic effects of clonidine in vivo. %Z https://katalog.bibliothek.tu-chemnitz.de/Record/ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTE1Mi9hanByZW5hbC4yMDAxLjI4MS40LmY2Nzk %U https://katalog.bibliothek.tu-chemnitz.de/Record/ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTE1Mi9hanByZW5hbC4yMDAxLjI4MS40LmY2Nzk