Abolition of the renin-releasing action of frusemide by acute renal denervation in dogs.

1. The effects of infusions of frusemide at low (0.05-0.1 mg.kg-1.min-1) and high (0.5-2.0 mg.kg-1.min-1) rates were studied on renin secretion and urinary outputs of sodium and potassium in anaesthetized dogs in which one kidney was removed and the remaining kidney was either innervated or denervated. 2. When the kidney was innervated, low rates of infusion of frusemide did not significantly affect renin secretion if urinary volume and sodium losses were replaced. Without replacement of urinary losses, renin secretion increased at sodium deficits of 0.7-0.9 mmol.kg-1 in the presence of elevated rates of sodium and potassium excretion. 3. High rates of infusion of frusemide caused an immediate increase in renin secretion from innervated kidneys which was not related to urinary losses. 4. Denervation of the kidney increased the urinary outputs of sodium and potassium while it decreased the rate of renin secretion to one-tenth of the resting value. 5. Denervation of the kidney abolished the renin-releasing action of frusemide at both low and high infusion rates even when the sodium deficit amounted to 4.3 mmol.kg-1. 6. Constriction of the aorta producing a fall of 10-30 mmHg in perfusion pressure raised the rate of renin secretion from denervated kidneys to control levels and partially restored the renin-releasing action of frusemide at high infusion rates. 7. The findings indicate that frusemide has a site of action apart from the macula densa in mediating renin release.