The proposed experiments will describe the molecular processes by which angiotensin II (AII) regulates transcription of the renin gene. The first specific aim will characterize the in vivo responsiveness of renin transcription to AII infusion. These studies will entail an assessment of renin transcription in salt-depleted and salt replete rats following infusion of either AII, ACE inhibitor or both. The results will then be correlated to changes in renin release as measured by PRA.
Specific aims 2 and 3 will assess the molecular basis for the acute and chronic regulation of renin expression by AII, respectively. These experiments will identify and characterize the modulation of putative transcriptional regulatory proteins which influence renin expression. Finally, specific aim 4 will entail cloning of these transcriptional regulatory factors. The cDNAs thus isolated will then be used for expression surveys. These studies should further elucidate the molecular events that govern regulation of renin expression.
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