SELECTIVE ANTAGONISM OF THE AT(1) 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 progress ion of renal disease. Angiotensin II, acting alone or in combination w ith other growth factors has been implicated in this process. The aims of this study were to identify the role of both angiotensin II and th e angiotensin receptor subtypes in DNA synthesis and protein synthesis in human renal proximal tubular cells. Primary cultures of human rena l 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 combinati on with losartan, PD123319 or 8-bromo-cAMP. Incubation of human proxim al tubular cells with angiotensin II (10(-10) M, 10(-8) M) induced a s ignificant early increase in [H-3]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 syn thesis was inhibited by 8-bromo-cAMP and losartan but not by PD123319, indicating that the responses are mediated via the AT, receptor and d ependent upon the inhibition of adenylate cyclase.