The kidney involvement in leptospirosis appears to be a special form of acute renal failure due to a higher frequency of polyuric forms and the presence of hypokalemia with an elevated urinary fractional excretion of potassium. Using a clearance technique, we detected higher fractional urinary potassium excretion in leptospirotic guinea pigs (26.5 ± 4.7%) than in normal animals (14.1 ± 2,8%, p < 0.05). After blocking distal NaCl reabsorption with furosemide, it was observed that in leptospirotic animals both fractional sodium excretion (40.0 ± 7.4%) and fractional potassium excretion (136.3 ± 32.7%) were higher than in normal animals (20.4 ± 3.8%, p < 0.05, and 43.6 ± 9.0%, p < 0.05, respectively). Microperfusion studies showed that the normal and leptospirotic medullary thick ascending limb had both identical transepithelial potential difference (+ 3.7 ± 0.4 vs. 3.9 ± 0.2 mV) and relative sodium-to-chloride permeability. The same technique showed that the osmotic water permeability (Posm; 0.9 ± 0.4 × 10-5 cm/s · atm) and diffusional permeability (34.7 ± 6.6 × 10”5 cm/s) observed in the leptospirotic inner medullary collecting duct (IMCD) in the presence of vasopressin were unchanged, as was also the case for urea permeability (3.74 ± 0.7×10-5 cm/s). These data show that acute renal failure in leptospirosis is characterized by tubular changes leading to potassium secretion probably due to a decrease in proximal sodium reabsorption. Furthermore, the inability to concentrate urine evidenced by the low Posm present in leptospirotic animals is due, at least in part, to IMCD resistance to vasopressin.
PGE2 inhibits osmotic water permeability ( P f) in the rat inner medullary collecting duct (IMCD) via cellular events occurring after the stimulation of cAMP, i.e., post-cAMP-dependent events. The α2-agonists also inhibit P f in the rat IMCD via post-cAMP-dependent events. The purpose of this study was to determine whether PGE2 plays a role in α2-mediated inhibition of P f, Na+, and urea transport in the rat IMCD. Isolated terminal IMCDs from Wistar rats were perfused to measure, in separate experiments, P f, lumen-to-bath22Na+ transport ( J lb), and urea permeability ( P u). Transport was stimulated with 220 pM arginine vasopressin (AVP) or 0.1 mM 8-(4-chlorophenylthio)-cAMP (CPT-cAMP). Indomethacin was used to inhibit endogenous prostaglandin synthesis, and the α2-agonists clonidine, oxymetazoline, and dexmedetomidine were used to test the role of PGE2 in the α2-mediated mechanism that inhibits transport. All agents were added to the bath. Indomethacin at 5 μM significantly elevated CPT-cAMP-stimulated P f, J lb, and P u, and subsequent addition of 100 nM PGE2 reduced these transport parameters. Indomethacin reversed α2 inhibition of CPT-cAMP-stimulated P f, J lb, and P u, and subsequent addition of PGE2 reduced transport in each case. Indomethacin partially reversed α2 inhibition of AVP-stimulated P f, J lb, and P u, and PGE2 reduced transport back to the α2-inhibited level. These results indicate that PGE2 is a second messenger involved in the mechanism of transport inhibition mediated by α2-adrenoceptors via post-cAMP-dependent events in the rat IMCD.
We examined the action of atrial natriuretic factor (ANF) on Na+ and Cl- transport in in vitro microperfused inner medullary collecting ducts (IMCD) isolated from rat kidneys. First we studied the isotopic fluxes at low perfusion rates (7 nl/min). The results showed that ANF added to bath decreased lumen-to-bath flux (Jl----b) of Na+ and increased Na+ bath-to-lumen flux (Jb----l). This was substantiated by a direct demonstration that ANF reduces net Na+ and Cl- absorption. The effect of ANF on Jl----b and Jb----l of Na+ was also observed at high perfusion rates (25 nl/min). The inhibitory effect of ANF was observed even when Na+ Jl----b was stimulated by vasopressin (VP). ANF (6 x 10(-11) M) added to bath increased Cl- Jb----l and generated a negative lumen potential difference (PD). These two effects were inhibited by furosemide and by the replacement of Na+ by choline and Cl- by SO4(2-) in the bath fluid. These observations are compatible with the existence of a Na(+)-Cl(-)-K+ cotransport mechanism stimulated by ANF. Moreover, the effects of guanosine 3',5'-cyclic monophosphate (cGMP) added to the bath on PD, Jl----b, and Jb----l of Na+ were similar to those observed with ANF. Thus, physiological concentrations of ANF inhibit directly Na+ and Cl- absorption in IMCD by two mechanisms, 1) by increasing cotransport Na(+)-Cl(-)-K+ secretion and 2) by inhibiting NaCl absorption both in the absence and in the presence of VP. These effects on NaCl transport appear to be mediated by cGMP.
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