The Significance of the Hairpin Counter-current Principle in the Pathogenesis of Toxic Kidney Lesions An Investigation of the Influence of Antidiuretic Hormone and Papaverine on Hydroxyquinoline Nephropathy of the Rat

Abstract

The influence of antidiuretic hormone (ADH) and papaverine on hydroxyquinoline-induced nephropathy in rats was tested, using enzyme histotopochemistry, enzyme activity measurement and morphometric investigation. Hydroxyquinoline causes a marked increase in renal weight, the development of wedge-shaped foci with severely dilated tubule segments, and a simultaneous reduction in dehydrogenases, alkaline phosphatase, and α-naphthyl esterase.

Both ADH and papaverine produced a significant inhibition of renal damage. The subjective findings were quantitatively confirmed by measurement of enzyme activity, using the microscope photometer, and by morphometric studies with the Leitz-Classimat (determination on the basis of the alkaline phosphatase reaction) of the surface percentage of brush border in the proximal tubules.

A disturbance of the hairpin counter-current system is to be considered as the cause of the renal lesion. This disturbance is caused by hydroxyquinoline-induced impairment of Na⁺/K⁺ transport, especially in the thick ascending limb of Henle’s loop.

Our results show that the hydroxyquinoline nephropathy can be favourably influenced both by stimulation of water re-absorption and possibly also transepithelial Na⁺ transport (ADH), and by increasing the blood flow of the arteriolae rectae with a resultant lowering of the intratubular urine concentration (papaverine).

The dependency of hydroxyquinoline nephropathy on the phylogenetically determined concentration capacity of the kidney, and the effective influencing of the condition by ADH and papaverine indicate the importance of the degree of efficiency of the medullary countercurrent system in the pathogenesis of this renal lesion.