Abstract
Since transmembrane sodium gradient is essential to many cell functions, there is continuing interest in methods that differentiate intracellular and extracellular Na^+^. In the kidney, shift reagent (SR) aided ^23^Na magnetic resonance spectros‐copy (MRS) has been successfully used only in isolated cells, tubules, and the perfused organ. In this report, we demonstrate for the first time that TmDOTP^5−^ can be used to distinguish Na^+^ compartments in kidneys in vivo. Infusion of 80 m__M__ TmDOTP^5−^ without added Ca^2+^ produced three resolved ^23^Na resonances, which we have assigned to intracellular Na^+^, vascular Na^+^, and intraluminal Na^+^. In comparison, infusion of 400 m__M__ DyTTHA^3−^ produced two broad and unresolved resonances. The ^31^P spectra of the cellular high energy phosphate metabolites indicate that TmDOTP^5−^ is safe for in vivo applications. Washout studies suggest that this SR displays renal clearance similar to that of MR imaging contrast agents. However, the glomerular filtration rate (GFR) in animals infused with TmDOTP^5−^ was reduced by 49% compared with the GFR in control animals, perhaps due to the hypotensive effects of the SR. We conclude that TmDOTP^5−^ is effectively cleared from the blood of live animals but that a different formulation will be required for clinical application.