Angiotensin II acts through the AT1 receptor to increase c-fos expression and phosphoinositide turnover in vascular smooth muscle cells, as these responses were abolished by losartan.
Angiotensin II mediates proto-oncogene expression and phosphoinositide turnover in vascular smooth muscle cells exclusively via the AT1 receptor, providing mechanistic insight into smooth muscle hypertrophy.
OBJECTIVES: The aim of this study was to determine which angiotensin II receptor (AT receptor) mediates proto-oncogene expression and phosphoinositide metabolism in vascular smooth muscle cells in vitro. DESIGN: The AT receptor antagonists DuP753 (losartan), an AT1 antagonist, and PD 123319, an AT2 antagonist, were used to characterize AT receptors on cultured vascular smooth muscle cells derived from the rat mesenteric artery and to identify which receptor subtype mediates the angiotensin II-induced increase in proto-oncogene expression and phosphoinositide metabolism. METHODS: Rat mesenteric artery vascular smooth muscle cells were grown using standard cell culture methods. Proto-oncogene induction was measured using Northern blotting. Phosphoinositide breakdown was assessed by measuring 3H-inositol phosphates released from prelabelled cells. RESULTS: Receptor-binding studies revealed that the AT1 receptor predominated on vascular smooth muscle cells. Incubation of quiescent cells with 0.1 mumol/l angiotensin II resulted in a 65% increase in total 3H-inositol phosphates released compared with unstimulated cells and in a rapid accumulation of c-fos messenger RNA (mRNA). Pre-incubation of the cells with 10(-5) mol/l PD 123319 had no effect on either total inositol phosphates release or c-fos mRNA induction. Both responses, however, were totally abolished by pre-incubation of the cells with 10(-5) mol/l losartan or saralasin. CONCLUSIONS: Angiotensin II acts through the AT1 receptor to increase c-fos expression and phosphoinositide turnover in vascular smooth muscle cells. These mechanisms may be important in angiotensin II-induced smooth muscle hypertrophy.
Lyall et al. (Tue,) reported a other. Angiotensin II with AT1 antagonist (losartan) or AT2 antagonist (PD 123319) vs. Unstimulated cells was evaluated on Proto-oncogene expression (c-fos mRNA) and phosphoinositide metabolism ([3H]-inositol phosphates release). Angiotensin II acts through the AT1 receptor to increase c-fos expression and phosphoinositide turnover in vascular smooth muscle cells, as these responses were abolished by losartan.