IDENTIFICATION OF A CONTRACTILE FUNCTION FOR RENAL MEDULLARY INTERSTITIAL-CELLS

Renomedullary interstitial cells (RMIC) are unique to the renal medull a, By virtue of their anatomic location and arrangement, RMIC may hind er axial dissipation of the concentration gradient, thereby aiding uri nary concentration, A more active role in urinary concentration has be en postulated on the basis of speculations about RMIC contractile pote ntial, however, RMIC contraction has not been investigated, To determi ne if these cells are contractile, cultured rat RMIC were exposed to e ndothelin-1 (ET-1), a potent vasoconstrictor which binds to RMIC, and examined using video microscopy, ET-1 (as low as 10 pM) caused a slowl y developing and dose-dependent reduction in RMIC surface area, ET-1 m arkedly increased the number and intensity of F-actin microfilament st aining, ET-l-induced RMIC contraction was not altered by nifedipine, w as partially reduced by nickel, and was completely inhibited by H7, in dicating that ET-1 action is mediated by protein kinase C and is parti ally dependent upon receptor-operated calcium channels, The ET-1 effec t does not involve nitric oxide since N-G-monomethyl-L-arginine did no t alter ET-1-induced RMIC contraction; in addition, ET-1 had only a mi nor effect on cGMP levels and no effect on nitrite production, PGE(2) acts in an autocrine manner to dampen ET action since indomethacin pot entiates, while PGE(2) inhibits, ET-1-induced RMIC contraction, The co ntractile response is not unique to ET-1 since vasopressin also reduce s RMIC surface area and increases F-actin microfiliment staining. Thes e studies demonstrate that RMIC in culture are contractile. The possib ility is raised that contraction of RMIC plays a role in modifying uri nary concentration as well as regulation of other renal medullary func tions.