EFFECTS OF ANGIOTENSIN-II ON CULTURED RAT RENOMEDULLARY INTERSTITIAL-CELLS ARE MEDIATED BY AT(1A) RECEPTORS

Renomedullary interstitial cells (RMICs) are prominent in the inner me dullary interstitium and have binding sites for several vasoactive age nts. including angiotensin II (ANG II). Although the functional role o f RMICs remains largely unknown, it is likely that the interaction bet ween RMICs and vasoactive peptides is important in the regulation of r enal function. The current investigation characterizes the cellular re sponses following treatment of RMICs with ANG II. Studies were perform ed on RMICs isolated from Sprague-Dawley rat kidneys. I-125-labeled [S ar(1),Ile(8)]ANG II specifically bound to RMICs at sites determined by reverse transcription-polymerase chain reaction to be of the AT(1A) s ubtype. ANG II (10(-6) and 10(-10) M) had no effect on either basal or forskolin-stimulated adenosine 3',5'-cyclic monophosphate accumulatio n in RMICs but increased intracellular inositol 1,4,5-trisphosphate co ncentration after 10 s and intracellular calcium concentration after 1 8 s. For RMICs plated at low densities, ANC; II (10(-6) M) induced an increase in [H-3]thymidine incorporation, mediated through the AT(1)-r eceptor subtype, For RMICs plated at high densities, ANG II (10(-6) M) induced an increase in Extracellular matrix synthesis as detected by trans-S-35 incorporation, an effect also mediated by AT(1) receptors. We conclude that ANG II AT(1A) receptors on cultured RMICs are coupled to intracellular second messenger pathways leading to hyperplasia and synthesis of extracellular matrix.