Angiotensin-II is a key factor in renal fibrosis. Obstructive nephropathy induces an isoform shift from catalytic Ampk alpha 2 towards Ampk alpha 1 which contributes to signaling involved in renal tissue injury. The present study explored whether the Ampk alpha 1 isoform contributes to the renal effects of angiotensin-II. To this end, angiotensin-II was infused by subcutaneous implantation of osmotic minipumps in gene targeted mice lacking functional Ampk alpha 1 (Ampk alpha(-/-)) and corresponding wild-type mice (Ampk alpha 1(+/+) ). Western blotting and qRT-PCR ciere employed to determine protein abundance and mRNA levels, respectively, in renal tissue. In Ampk alpha 1(+/+) mice, angiotensin-II increased renal Ampk alpha 1 protein expression without significantly modifying renal Ampk alpha 2 protein expression. The renal phosphorylated Ampk alpha (Thr(172)) protein abundance was not affected by angiotensin-II in neither genotypes, but was significantly lower in Ampk alpha 1(-/-) mice than Ampk alpha 1(+/+) mice. Angiotensin-II increased the phosphorylation of Tak1 (Ser(412)) in renal tissue of Ampk alpha 1(+/+) mice, an effect virtually absent in the Ampk alpha 1(-/-) mice. Furthermore, angiotensin-II treatment significantly increased renal protein and mRNA expression of alpha-smooth muscle actin (alpha Sma) as well as Takl-target gene expression: Cox2, Il6 and Pail in Ampk alpha 1(+/+) mice, all effects significantly less pronounced in Ampk alpha 1(-/-) mice. In conclusion, angiotensin-II up regulates the Ampk alpha 1 isoform in renal tissue. Ampk alpha 1 participates in renal Tak1 activation and Tak1-dependent signaling induced by angiotensin-II. (C) 2016 Elsevier Inc. All rights reserved.