Localization and functional properties of angiotensin II AT1 receptors in the kidney: Focus on renomedullary interstitial cells

Abstract

The renal medulla plays an important role in maintaining body fluid and electrolyte balance and long-term blood pressure homeostasis through its unique structural and functional properties. Among several humoral, paracrine factors or autocoids, angiotensin II (Ang II) has been implicated in the regulation of renal medullary function, including the medullary/papillary microcirculation, urine concentration, and blood pressure, but the mechanisms by which Ang II exerts influences in the renal medulla are largely unknown. The purpose of this review is to summarize the cellular localization, regulation, and function-al properties of Ang II AT1 receptors in the kidney, with special emphasis on type I renomedullary interstitial cells (RMICs) in the renal medulla and cultured RMICs. High densities of AT1 receptors have been localized in type I RMICs in the inner stripe of the outer medulla by high resolution light and electron microscopic autoradiography following in vitro or in vivo labelling, or in cultured RMICs. Furthermore, reverse transcription polymerase chain reaction and Southern blot analysis now confirm that AT1 receptors in cultured RMICs are exclusively of the AT1A subtype. In cultured RMICs, Ang II markedly increases intracellular inositol 1,4,5-triphosphate (IP3) concentration, and stimulates cell proliferation and extracellular matrix synthesis, and these cellular responses are exclusively mediated by AT1 receptors. Considering the co-occurrence of high levels of renin, renin substrate angiotensinogen, and Ang II in the interstitial fluid compartment, and AT1 receptors in type I RMICs of the renal medulla, the AT1 receptor-bearing RMICs may be more responsive to the locally formed interstitial Ang II than to the circulating peptide. Since RMICs also contain the receptors for other vasoactive peptides, such as endothelin (ETA and ETB), natriuretic peptides (NPRA and NPRB), and bradykinin (B2), and synthesize prostaglandins and medullipins, they may serve as an important site for functional interactions between Ang II and other vasoactive peptides in modulating renal medullary function. More studies using different experimental approaches are therefore required to explore and elucidate the functional role of renal interstitial Ang II and AT1 receptors in RMICs in the physiological control of renal medullary function and in the pathophysiology of hypertension and progressive renal diseases.