Ls. Wang et al., SYNERGISTIC EFFECT OF DEXAMETHASONE AND ISOPROTERENOL ON THE EXPRESSION OF ANGIOTENSINOGEN IN IMMORTALIZED RAT PROXIMAL TUBULAR CELLS, Kidney international, 53(2), 1998, pp. 287-295
To investigate whether the expression of angiotensinogen (ANG) in rat
kidney proximal tubules is stimulated by dexamethasone and isoproteren
ol, immortalized rat proximal tubular cells (IRPTC) were cultured in a
monolayer. Immunoreactive rat ANG (IR-rANG) in the culture medium was
measured by a specific radioimmunoassay (RIA) for rANG. This RIA was
developed by employing rabbit antiserum against the purified recombina
nt rat ANG (rANG). The purified rANG from plasma and the iodinated rAN
G were used as the hormone standard and tracer, respectively. The RIA
is specific for rat ANG and it has no cross-reactivity with other pitu
itary hormone preparations or other rat plasma proteins. The sensitivi
ty of detection of the RIA is approximately 2 ng of rANG. The levels o
f IR-rANG in the culture media of IRPTC ranged from 2 to 5 ng/ml/24 hr
/10(6) cells. The addition of dexamethasone (10(-13) to 10(-5) M) stim
ulated the expression and secretion of rANG from IRPTC in a dose-depen
dent manner, whereas the addition of isoproterenol alone had no effect
. However, a combination of both dexamethasone and isoproterenol syner
gistically stimulated the expression and secretion of rANG by IRPTC. T
he synergistic effect of dexamethasone and isoproterenol was blocked b
y the presence of RU 486 (a glucocorticoid receptor antagonist) or pro
pranolol (beta-adrenoceptor blocker). These studies suggest that the a
ddition of dexamethasone and isoproterenol acts synergistically to sti
mulate the expression and secretion of ANG protein in rat proximal tub
ules in vivo.