Angiotensin II stimulates cellular hypertrophy of LLC-PK1 cells through the AT1 receptor.
We have investigated possible growth-promoting effects of angiotensin II (ANG II) in the pig tubular epithelial cell line LLC-PK1. 10(-6)-10(-10) M ANG II inhibited proliferation as measured by [3H]thymidine incorporation. However, the same concentration of peptide induced tubular hypertrophy as assessed by increases in de novo protein synthesis, total protein, and RNA content. These effects were mediated through AT1 receptors. Furthermore, LLC-PK1 cells exhibited specific binding sites for ANG II and expressed mature mRNA for the vascular smooth muscle AT1 receptor. ANG II incubation of cells significantly lowered intracellular cAMP, and the hypertrophogenic action of ANG II was abolished by co-incubation with the relative stable analogue dibutyryl-cAMP, suggesting the involvement of intracellular nucleotides in the signal-transduction processes leading to hypertrophy. Our results collectively suggest that ANG II is a hypertrophogenic growth factor for LLC-PK1 cells. Considering the importance of tubular hypertrophy in the progression of renal failure in many models, strategies to block the action of ANG II on tubular cells may offer an attractive alternative way to control deterioration of renal function besides modulation of haemodynamics.
Wolf
G
G
Department of Medicine, University of Frankfurt, Frankfurt am Main, Germany.
Zahner
G
G
Mondorf
U
U
Schoeppe
W
W
Stahl
R A
RA
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology; D006984:Hypertrophy; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011506:Proteins / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis; D011945:Receptors, Angiotensin / Q000145:classification / Q000187:drug effects* / Q000378:metabolism
D006133:Growth Substances; D011506:Proteins; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D012313:RNA; D000242:Cyclic AMP