Protein kinase C and protein kinase A regulate the expression of angiotensin II receptor mRNA in smooth muscle cells.

Using reverse transcription polymerase chain reaction and fura-2 microfluorometry of intracellular Ca2+ concentrations, we investigated the effects of angiotensin II and cyclic AMP on the expression of angiotensin II type 1 receptor mRNA and the relationship between angiotensin II receptor mRNA level and physiological responsiveness in rat aortic smooth muscle cells in primary culture. Angiotensin II (1 microM) induced a time- and dose-dependent transient decrease in the level of angiotensin II receptor mRNA. The maximal decrease (50 +/- 13% of control) occurred at 6 h, followed by a gradual return to the control level within 24 h. H-7 (30 microM), a relatively specific protein kinase C inhibitor, inhibited decrease in the expression of angiotensin II receptor mRNA induced by 6 h angiotensin II treatment, while 6 h stimulation by 0.3 microM phorbol 12-myristate 13-acetate also induced a decrease (35 +/- 8% of control) in the expression of angiotensin II receptor mRNA. An increase in cellular cyclic AMP induced by 10 microM forskolin plus 10 microM 3-isobutyl-1-methyl-xanthine, decreased the angiotensin II receptor mRNA level to 50 +/- 13% of the control at 6 h and increased it to 219 +/- 39% of the control at 48 h of treatment. Angiotensin II-induced decrease and cyclic AMP-induced increase in the expression of angiotensin II receptor mRNA were accompanied by a reduction and enhancement in [Ca2+]i transients induced by angiotensin II, respectively. In contrast with angiotensin II receptor mRNA level (102 +/- 8% of control), the [Ca2+]i transients were markedly decreased in angiotensin II plus H-7 treated cells.(ABSTRACT TRUNCATED AT 250 WORDS)