In the pase decade, several experimental models of acute renal failure (ARF) have been evaluated with micropuncture and hemodynamic techniques. Five of these models have been most extensively studied: glycerol injection, renal artery clamping, intrarenal norepinephrine infusion, uranyl nitrate, and mercuric chloride administration. In the first three models, renal ischemia is the initiating insult, whereas in the two nephrotoxic models a direct effect of the agent on cellular integrity is also seemingly operative. In all of these models, renal blood flow 24--48 h after the initial insult either spontaneously returns to normal or can be elevated to this level with volume expansion but without restoration of the glomerular filtration rate. Therefore, the maintenance of ARF in these various models is due to other factors, which include tubular obstruction, leakage of filtrate across damaged tubular epithelium, and a decrease in the glomerular capillary ultrafiltration coefficient. In a given model, one or all three of these alterations may be present. Although these various models may not be completely analogous to the clinical setting, they have provided powerful tools for the study of ARF and their use has greatly increased our knowledge in this field.

No abstract

No abstract

Deterrence theories purport to supply the auxiliary assumptions rational choice theories need to predict rational strategic behavior. They generally assume that would-be initiators are (i) instrumentally rational; (2) risk-prone gain-maximizers; (3) free of domestic constraints; and (4) able to identify themselves correctly as defenders or challengers. These assumptions are contradicted by empirical studies that indicate that risk-prone, gain-maximizing initiators are relatively uncommon; that leaders at times calculate as deterrence theories expect, but behave contrary to their predictions; and that the calculus of initiators generally depends on factors other than those identified by deterrence theories. Deductive theories of deterrence are also inadequate because they do not define their scope conditions. Nor can they accommodate deviation by initiators from processes of rational calculation. Rational deterrence theories are poorly specified theories about nonexistent decision makers operating in nonexistent environments.

A B S T R A C T In a previous study we have found that acetylcholine, a renal vasodilator, inhibits fractional and absolute reabsorption of sodium in the proximal tubule of the dog. To delineate whether this effect on proximal tubular sodium reabsorption was related to alterations in renal hemodynamics or to a direct tubular action of the drug, free-flow micropuncture studies were performed in the dog in which the tubular fluid to plasma inulin ratio and nephron filtration rate were determined before and during the administration of a structurally different renal vasodilator, bradykinin. This agent increased sodium excretion from 12 to 96 *Eq/cnin and decreased total kidney filtration fraction from 0.35 to 0.25. However, sodium reabsorption in the proximal tubule of the superficial nephrons was unchanged during bradykinin 'administration.Since it has been shown that a decrease in filtration fraction and presumably peritubular capillary protein concentration will decrease proximal tubular sodium reabsorption, studies were performed to determine whether the fall in total kidney filtration fraction seen with both vasodilators is paralleled by a similar change in the circulation of superficial nephrons. The results of these studies indicate that neither agent altered superficial nephron capillary protein concentration, hematocrit, or filtration fraction.

Studies were performed in the dog to determine the mechanism of the renal functional impairment which follows the administration of the nephrotoxic agent, uranyl nitrate. In the first series of 28 experiments, total renal blood flow was determined with the radioactive microsphere method before and after uranyl nitrate administration, 10 mg/kg. Total blood flow fell from 199 to 121 ml/min 6 hr after administration of uranyl nitrate (P less than 0.001) but was unchanged 48 hr after administration of the drug. Yet the blood urea nitrogen concentration had increased from a control value of 13 to 120 mg/100 ml at 48 hr (P less than 0.001). Since renal blood flow was normal at 48 hr, micropuncture studies were performed to further evaluate the mechanism of the renal impairment. In the first group of nine studies using a 10 mg/kg dose of uranyl nitrate, nephron glomerular filtration rate (GFR) was reduced 37% while total kidney GFR averaged less than 1% of normal. A similar disparity between superficial and total GFR was noted after a 5 mg/kg dose even though urine flow was comparable to values found in normal hydropenic dogs. Proximal tubular transit time and intratubular pressure were normal. The recovery of 3H-inulin injected into the proximal tubule was 97% in normal dogs and 14% in uranyl nitrate dogs (P less than 0.001). Since there was no difference between early and late proximal tubular nephron GFR, it was suggested that the pars recta, the segment most severely involved histologically, was the main site of inulin leak. Scanning electron microscopy revealed an alteration in epithelial architecture which may have accounted, at least in part, for the diminution in nephron GFR. These studies are interpreted to indicate that the impairment in renal function in this model is due to both leakage of filtrate across damaged tubular epithelium and a modest decrease in nephron GFR.

No abstract

A B S T R A C T Studies were performed to determine the effect of decreased endogenous release of renal prostaglandins on urinary sodium excretion. Two structurally dissimilar inhibitors of prostaglandin synthesis were employed, and studies were performed in conscious dogs allowed to recover from prior surgical instrumentation. Either meclofenamate (2 mg/kg) or the competitive prostaglandin inhibitor RO 20-5720 (1 mg/kg) was given to seven unanesthetized dogs undergoing a water diuresis. The administration of either prostaglandin inhibitor did not alter glomerular filtration rate, renal plasma flow, urinary volume, or potassium excretion. Sodium excretion, however, increased from 32 to 130 ueq/min (P <0.02). Essentially, the entire increase in sodium excretion was due to an increase in urinary sodium concentration from 7.7 to 28.3 meq/liter (P < 0.02). On a different day, the same animals were studied before and after administration of the diluent of the prostaglandin inhibitor. No change was noted in sodium excretion or any other parameter.Thus, these findings suggest that prostaglandin inhibition in the conscious dog is associated with a natriuresis without a change in urinary volume or potassium excretion during water diuresis. This may indicate that the natriuresis was due to diminished sodium reabsorption beyond the distal tubule.