The effect of angiotensin on cation transport by rat kidney cortex slices

1. A study has been made of the effect of angiotensin (10(-12) g/ml.) on active and passive transport of sodium, potassium and water between rat kidney cortex slices and the incubation medium.2. Angiotensin has no effect on the passive uptake of sodium and loss of potassium by slices incubated under conditions which inhibit active transport.3. Active sodium extrusion by slices incubated under aerobic conditions is stimulated, whereas active potassium uptake is inhibited by angiotensin.4. Sodium pump activity is stimulated by angiotensin in the presence of ouabain or in the absence of potassium in the incubation medium, conditions which block the sodium for potassium exchange pump.5. There is a 2 min latent period following the application of angiotensin before a response is observed.6. These findings are discussed in relation to the mechanism of action of angiotensin on kidney sodium and fluid transport processes.     

Relationship between PAH transport and Na-K-ATPase activity in the rabbit kidney.

The relationship between Na-K-ATPase activity and p-aminohippurate (PAH) transport was examined in renal cortical slices of mixed-breed rabbits by using ouabain to vary the level of Na-K-ATPase activity. Ouabain increased passive PAH uptake, measured in the presence of probenecid. Slice homogenate Na-K-ATPase activity was inhibited by 50% with about 2 X 10(-6) M ouabain. When the concentration was 10(-5) M or above, active PAH uptake was inhibited. Lower concentrations (10(-7) and 10(-6) M) of ouabain stimulated active PAH uptake. Acetate stimulated PAH uptake when medium ouabain was less than 10(-4) M. Ouabain, 10(-5) M and higher, caused intracellular K+ to fall and Na+ to rise. The changes in active PAH uptake observed with ouabain correlated much better with changes in intracellular K+ or Na+ levels (P less than 0.01) than with changes in slice homogenate Na-K-ATPase activity. Vmax for active PAH uptake decreased with 5 X 10(-5) M ouabain, and tended to increase with 10(-7) M ouabain. Ouabain did not alter Km for active PAH uptake. The data support the hypothesis that there is a functional link between active PAH transport and Na-K-ATPase activity. This linkage may be an indirect one mediated by changes in intracellular cation concentrations.     

Monovalent cation conductance of the sustained inward current in rabbit sinoatrial node cells

 Under the whole cell clamp, superfusion of the rabbit sinoatrial node cells with a Na⁺-free solution suppressed the sustained inward current (I_st), and the L-type Ca²⁺ current (I_Ca,L) could be recorded on depolarization less negative than –40 mV from the holding potential of –80 mV. On the other hand, replacement of Ca²⁺ with Mg²⁺ in the external solution suppressed inward-going I_Ca,L and isolated I_st. Under this condition, I_st measured as a nicardipine-sensitive current showed an activation threshold between –60 and –70 mV. The conductance sequence of I_st for monovalent ions was determined as Na⁺ > Li⁺ >> K⁺ @ Cs⁺ by replacing the external Na⁺ with these alkali metal ions. The contribution of I_st to the diastolic depolarization is discussed. Received: 12 June 1996 / Received after revision: 31 July 1996 / Accepted: 7 August 1996     

Effect of osmotic shocks on rabbit kidney cortex slices

Rabbit kidney cortex slices behave an osmometers when withstanding hyperosmotic or hyposmotic shocks of amplitude up to pi 1/pi 2 = 1.25. For hyposmotic shocks of amplitude larger than or equal to pi 1/pi 2 = 1.50, the maximum swelling achieved is less than what can be expected on the basis of the van't Hoff relation, thereby indicating that a volume regulation process is taking place. Volume regulation in kidney slices can be dissociated into two distinct phases. The first one, of swelling limitation, is very rapid and keeps maximum cell volume at values lower than expected when the tissue is considered as an osmometer. This phase is followed by a slow volume readjustment process during which volume progressively decreases towards control values. The major intracellular osmotic effector loss during both swelling limitation and volume readjustment is Na+. The overall volume regulation process is insensitive to furosemide, vanadate, and bumetanide. Swelling limitation is blocked by addition of ouabain. Contrary to what has been believed previously, there is, however, no need to implicate control of the activity of a ouabain-sensitive, Na+/K+ pump in the Na-dependent volume regulation mechanism.     

Lithium carbonate and the problem of kidney damage. Intracellular effects in rat kidney slices

Histological lesions in man, presumably indicating kidney damage, may occur during therapy with lithium carbonate. We studied the cellular effects of lithium carbonate applied in vitro to slices of kidney from adult female Sprague-Dawley rats. Alternate slices were immersed in saline solution containing 1.1 mEq/L of lithium carbonate; the other slices were immersed in ordinary saline solution as controls. Compared with control specimens, a two-hour incubation in lithium carbonate solution showed (1) with toluidine blue 0, in the cells of the collecting ducts a fibrous metachromatic network that was interpreted as indicating microtubule bundles; and (2) with Brookes' stain in the proximal convolutions, increased acidophilia of the hyaline droplets and of the nucleus that implied interaction of lithium carbonate with the protein transport and degradation mechanism located in these cells. The results can be interpreted as being due to polymerizations or to conformational changes of protein components caused by lithium. These changes are consistent with altered functions of the kidney observed in manic-depressive patients receiving treatment with lithium carbonate, which lead to polyuria (collecting ducts) and may lead to nephrotoxicity (proximal convolutions).     

Monovalent cation specificity of passive transport mediated by laidlomycin and 26-deoxylaidlomycin

The capacity of laidlomycin (I) and the new 26-deoxylaidlomycin (II) to facilitate passive fluxes of cations through a layer of organic solvent (CHCl3/n-heptane) was estimated in comparison to monensin A (III). While II displayed a 10fold higher transport rate for sodium as compared to calcium, laidlomycin (I) was distinguishable by mediating approx. 100 times lower conveyance of the divalent cations.