NUCLEAR ANGIOTENSIN RECEPTORS INDUCE TRANSCRIPTION OF RENIN AND ANGIOTENSINOGEN MESSENGER-RNA

The observation that nuclei from hepatic tissue exhibit specific angio tensin II (Ang II) binding led us to explore whether Ang II modulates mRNA in general, mRNA specific for renin system components, or both. N uclei from hepatic tissue exhibited a single high-affinity (K(d)=0.4 n mol/L) Ang II-specific binding site, which was associated with increas ed RNA transcription. Whereas total RNA extracted from nuclei increase d 1.5-fold in response to Ang II (10(-9) mol/L), specific mRNA for ren in and angiotensinogen increased 7.8- and 2.5-fold, respectively. Ang II binding and induced transcription showed parallel Ang II dose respo nses that were both inhibited by 10(-5) mol/L DuP 753 or saralasin. Ma ximum Ang II binding and RNA transcription occurred at the same Ang II concentration (10(-9) mol/L). Higher doses of Ang II resulted in a pr ogressive decrease in RNA transcription. Together, these results demon strate that hepatic nuclei have functional Ang II-specific receptors. It is concluded that Ang II may elicit responses at nuclear receptors, which heretofore were associated only with Ang II receptors located o n plasma membranes. However, the individual contribution of plasma and nuclear membrane Ang II receptors to the overall cellular Ang II tran scriptional response and their possible interactions remain to be dete rmined.