Selective antagonism of the AT₁ receptor inhibits angiotensin II stimulated DNA and protein synthesis in primary cultures of human proximal tubular cells

The hypertrophy of renal proximal tubular cells occurs as an adaptive response to a variety of stimuli and may be involved with the progression of renal disease. Angiotensin II acting alone or in combination with other growth factors has been implicated in this process. The aims of this study were to identify the role of both angiotensin II and the angiotensin receptor subtypes in DNA synthesis and protein synthesis in human renal proximal tubular cells. Primary cultures of human renal proximal tubular cells were incubated with angiotensin II (10^-10 M 10^-8 M, 10^-6 M) for 24 to 120 hours either alone or in combination with losartan, PD123319 or 8-bromo- cAMP. Incubation of human proximal tubular cells with angiotensin II (10^{- 10} M, 10^-8 M) induced a significant early increase in [³H]thymidine uptake by 19% and 56% (P < 0.01), respectively, and a later increase in total protein content by 30% (P < 0.01). The effect of angiotensin II upon DNA and protein synthesis was inhibited by 8-bromo-cAMP and losartan but not by PD123319, indicating that the responses are mediated via the AT₁ receptor and dependent upon the inhibition of adenylate cyclase.