Effects of various transport inhibitors on oscillating TGF pressure responses in the rat

The present study examines the effect in free flow microperfusion experiments of various diuretics with different sites of action on an oscillating tubular pressure response to changes in Henle loop flow rate. Amiloride (1 mM) and bendroflumethiazide (0.1 mM) had no effect outside the stimulation caused by the solvent (Ringer solution). Acetazolamide (0.5 mM) stimulated a slow (30 mHz) oscillation and often activated a fast (130-190 mHz) rhythm. Furosemide (FUR) (0.1-2.0 mM) abolished the slow oscillation and caused the intratubular pressure to rise by 2-3 mm Hg. FUR (0.05 mM) caused partial inhibition of the slow rhythm, which usually became irregular. Bumetanide (BUM) (0.05 mM) elicited a biphasic response. Initially the pressure decreased, while the slow rhythm was amplified; then the fast oscillation was activated; after 4-6 min the oscillations disappeared, while the pressure increased. In the recovery period the oscillations often became irregular. The results confirm that the oscillating pressure response is mediated by a transport function of the macula densa (MD); and, thus, has the character of a tubulo-glomerular feedback (TGF) response. The data suggest 1. that BUM inhibition of NaCl co-transport in the cortical thick ascending limb of Henle (TAL) is delayed as compared to the medullary TAL; and 2. that FUR action at the MD interferes with more than one carrier mechanism. Partial inhibition gives rise to irregular oscillations.