Key Points
- To determine whether the growth and proliferative effects of intracellular angiotensin II depend on the angiotensin II type 1 (AT1) receptor.
- Evaluated native Chinese hamster ovary (CHO) cells and CHO cells stably expressing the AT1 receptor (CHO-AT1) following transient or stable transfection with intracellular angiotensin II (iANG II) expression vectors.
- Measured cell proliferation in serum-free medium via cell counts every 24 hours up to 72 hours and Wst-1 viability assays in the presence or absence of extracellular angiotensin II and AT1 receptor antagonists (losartan, valsartan, telmisartan, and candesartan).
- Transient and stable expression of iANG II significantly enhanced proliferation in both CHO and CHO-AT1 cells compared to controls, whereas extracellular angiotensin II stimulated growth only in cells expressing the AT1 receptor.
- The AT1 receptor antagonists losartan, valsartan, telmisartan, and candesartan failed to attenuate iANG II-induced cell proliferation, even though losartan selectively blocked growth stimulated by extracellular angiotensin II.
Structured PICO
PPopulationNative Chinese hamster ovary (CHO) cells and CHO cells stably transfected with AT1 receptor (CHO-AT1)
IInterventionIntracellular angiotensin II (iANG II) expression vector (transient and stable transfection)
CComparatorScrambled peptide transfection or non-transfected cells
OOutcomeCell proliferation (measured by cell counting every 24 h up to 72 h and Wst-1 assay)surrogate
Intracellular angiotensin II induces cell proliferation independent of AT1 receptors, suggesting novel intracellular mechanisms of action for ANG II.