Identification of a contractile function for renal medullary interstitial cells.

Abstract

Renomedullary interstitial cells (RMIC) are unique to the renal medulla. By virtue of their anatomic location and arrangement, RMIC may hinder axial dissipation of the concentration gradient, thereby aiding urinary concentration. A more active role in urinary concentration has been postulated on the basis of speculations about RMIC contractile potential, however, RMIC contraction has not been investigated. To determine if these cells are contractile, cultured rat RMIC were exposed to endothelin-1 (ET-1), a potent vasoconstrictor which binds to RMIC, and examined using video microscopy. ET-1 (as low as 10 pM) caused a slowly developing and dose-dependent reduction in RMIC surface area. ET-1 markedly increased the number and intensity of F-actin microfilament staining. ET-1-induced RMIC contraction was not altered by nifedipine, was partially reduced by nickel, and was completely inhibited by H7, indicating that ET-1 action is mediated by protein kinase C and is partially dependent upon receptor-operated calcium channels. The ET-1 effect does not involve nitric oxide since NGmonomethyl-L-argiinine did not alter ET-1-induced RMIC contraction; in addition, ET-1 had only a minor effect on cGMP levels and no effect on nitrite production. PGE2 acts in an autocrine manner to dampen ET action since indomethacin potentiates, while PGE2 inhibits, ET-1-induced RMIC contraction. The contractile response is not unique to ET-1 since vasopressin also reduces RMIC surface area and increases F-actin microfiliment staining. These studies demonstrate that RMIC in culture are contractile. The possibility is raised that contraction of RMIC plays a role in modifying urinary concentration as well as regulation of other renal medullary functions. (J. Clin. Invest. 1995. 96:411-416.)

Countercurrent exchange in the renal medulla

“…That arrangement might augment concentrating ability by preventing dissipation of axial NaCl and urea gradients within the interstitium (58). Renomedullary interstitial cells are contractile (37) and the possibility that contraction and relaxation of these cells could alter transport properties or vascular resistance cannot be ruled out. Even if they do not modulate transport functions, it is possible that their stacking isolates slitlike regions of interstitium through which the parallel structures present in the inner medulla must exchange (58,59,74,(125)(126)(127).…”

Localization and Functional Properties of Angiotensin II AT1 Receptors in the Kidney. Focus on Renomedullary Interstitial Cells.

“…In vitro, prostaglandin biosynthesis is stimulated by Ang II (18, 19) and cGMP is increased by ANP in cultured RMICs (22). Furthermore, ET causes contraction of cultured RMICs in vitro as does vasopressin (26). Thus, accumulating evidence indicates that RMICs have the potential to respond to stimulation by multiple vasoactive peptides and exhibit a range of biological events.…”

The effects of different inhibitory pathways of prostaglandin E2 biosynthesis on renomedullary interstitial cells in rats: a multidisciplinary study

“…RMICs are often arranged in rows between the loops of Henle and vasa recta, with their long axes being perpendicular to those of adjacent tubules and vessels, thus resembling the rungs of a ladder [3]. This anatomic arrangement suggests that RMICs may play an important role in maintaining urinary concentrating ability via preventing the axial diffusion in concentration gradient [5,6]. Studies demonstrate that the transplants of fragments from the renal medulla or of the cultured RMICs reverse renoprival hypertension [1,[7][8][9][10][11][12][13].…”