Angiotensin II causes mesangial cell hypertrophy.
Angiotensin II, a potent vasoconstrictor and known growth factor for vascular smooth muscle cells, has been implicated in the development of glomerulosclerosis. Because mesangial cell growth plays a critical role in the glomerulosclerotic process, the objective of this study was to determine the direct effect of long-term (48-hour) angiotensin II treatment on the growth of cultured murine mesangial cells. Subconfluent, quiescent adult murine mesangial cells were treated for 48 hours with media containing angiotensin II with and without its specific inhibitor losartan. In comparison to cells treated with serum-free medium, cells treated with serum plus insulin demonstrated a significant increase in cell number (1.93 +/- 0.1 times control, p < 0.05), [3H]thymidine incorporation per 10(5) cells (2.29 +/- 0.12 times control, p < 0.05), [3H]leucine incorporation per 10(5) cells (1.81 +/- 0.18 times control, p < 0.05), and total protein content per 10(5) cells (1.65 +/- 0.07 times control, p < 0.05). In contrast, cells treated with angiotensin II (10(-6) M) had no significant increase in cell number (0.84 +/- 0.01 times control) or [3H]thymidine incorporation per 10(5) cells (1.23 +/- 0.12 times control) but demonstrated a significant increase in [3H]leucine incorporation per 10(5) cells (1.61 +/- 0.09 times control) and total protein content per 10(5) cells (1.38 +/- 0.04 times control). Pretreatment with losartan blocked 56% of the angiotensin II-induced increase in [3H]leucine incorporation and 84% of the angiotensin II-induced increase in total protein content.(ABSTRACT TRUNCATED AT 250 WORDS)
Anderson
P W
PW
Department of Internal Medicine, Los Angeles County and University of Southern California Medical Center 90033.
Do
Y S
YS
Hsueh
W A
WA
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006984:Hypertrophy; D051379:Mice; D014176:Protein Biosynthesis; D011506:Proteins / Q000032:analysis
D011506:Proteins; D000804:Angiotensin II; D004247:DNA