NMR Studies of Renal Metabolism: Regulation of Renal Function by ATP and pH a

The function of the kidney is to maintain the volume and composition of the extracellular fluid. This is achieved by glomerular filtration and selective reabsorption of solutes and water by the renal tubular epithelium. Extracellular fluid volume is maintained by tubular reabsorption of sodium. The kidney regulates acid-base homeostasis by reabsorption of bicarbonate and excretion of acid into the urine. It is generally accepted that the energy for active transport by the renal tubules is provided in the form of ATP.' Although a variety of physical and humoral factors regulate renal function, inhibition of oxidative phosphorylation has been shown to inhibit sodium transport.'-" Furthermore, it has been suggested that the hormone aldosterone stimulates sodium reabsorption by increasing the production of ATP by oxidative phosphoryIation.'.'* The excretion of H + into the urine is largely controlled by varying the production of ammonia produced from the metabolism of glutamine. Despite considerable investigation, the primary signal that regulates renal ammoniagenesis is not completely understood." Nevertheless, previous investigators have suggested that the intracellular pH (pH,) of the renal tubular cell may be an important regulator of renal ammoniagenesis." Nuclear magnetic resonance spectroscopy has been used by many investigators to study the metabolism of a variety of organs including the kidney. Ross, Radda, and their colleagues14 pioneered "P N M R studies of perfused rat kidneys and the kidney in vivo. The goal of the present experiments was to utilize 31P N M R to investigate the role of pHi in the regulation of renal ammoniagenesis and to determine the importance of renal ATP in the regulation of sodium transport.