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 medullary interstitium and have binding sites for several vasoactive agents. including angiotensin II (ANG II). Although the functional role of RMICs remains largely unknown, it is likely that the interaction between RMICs and vasoactive peptides is important in the regulation of renal function. The current investigation characterizes the cellular responses following treatment of RMICs with ANG II. Studies were performed on RMICs isolated from Sprague-Dawley rat kidneys. I-125-labeled [Sar(1),Ile(8)]ANG II specifically bound to RMICs at sites determined by reverse transcription-polymerase chain reaction to be of the AT(1A) subtype. ANG II (10(-6) and 10(-10) M) had no effect on either basal or forskolin-stimulated adenosine 3',5'-cyclic monophosphate accumulation in RMICs but increased intracellular inositol 1,4,5-trisphosphate concentration after 10 s and intracellular calcium concentration after 18 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)-receptor 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.