摘要:

In the acute phase of ischemic renal failure, the severe depression of the glomenrlar jiltration rate (GFR) is due to obstruction of the tubules by cells and cell debris rejectedfrom the proximal tubules, a blockade which can be prevented at least partly, by treatment with osmotic diuretics. The isosthenuria, the second typical sign in ischemic acute renal failure, probably derives from the medullary ischemia that results from an intracapillary trapping of red cells. This, in turn, is suggested to be caused by oxygen-derived free radicals, which via increasing the capillary macromolecular permeability result in a massive extravasation of plasma and hence in hemoconcen-tration. As expectedfrom this hypothesis, scavengers may ameliorate both the trapping and the consequent medullary ischemia. Unfortunately, however, a therapy using both osmotic diuretics and scavengers fails to improve the long-term outcome. Hemodilution would seem more promising, since it will both prevent the medullary ischemia seen in the acute phase and substantially improve the long-term outcome. At a hematocrit of 0.30, rat kidneys exposed to 45-min ischemia will show a GFR I month after the insult of more than 50% of the normal GFR as against 15% in untreated animals.

ISSN:0886-022X    

DOI:10.3109/08860229209106632

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Mammalian cells differ considerably in the duration of anoxia which they can tolerate despite the fact that dramatic bioenergetic changes occur rapidly. Previous studies indicate that the ability to tolerate anoxia is at least partly due to an endogenous signal transduction system that senses O2 deficiency and signal altered ion transport functions in the mitochondria. The responses included inhibition of AT? synthase, ADP/AT? exchange, inorganic phosphate uptake, mitochondrial swelling, and loss of the mitochondrial proton-motive force. An important distinction between KCN toxicity and anoxia is that KCN does not elicit these protectve mechanisms. Thus, the ability of a compound to elicit these mechanisms in KCN-treated cells provides an assay for potential agonists of the endogenous protective mechanisms.

ISSN:0886-022X    

DOI:10.3109/08860229209106633

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Functionally similar ischemic acute renal failure (ARF), as estimated by glomerular jltration rates (GFR), was induced by renal artery clamping (RAC) or intrarenal norepinephrine (NE) in rats and renovascular reactivity was examined at 1 week. With RAC-ARF induction there was total renal ischemia followed by abrupt return of renal blood jlow (RBF). With NE-ARF induction there was subtotal ischemia (10-15% of basal RBF) with RBF recovery over several hours. Renovascular resistance (RVR) did not change to renal perfusion pressure (RPP) reduction in the autoregulatory range in RAC-ARF but paradoxically increased in NE-ARF. fiere was an exaggerated response to renal nerve stimulation in NE-ARF but no response in RAC-ARF. fiere was a vasoconstrictor response to intrarenal norepinephrine in the former but a negligible response in the latter. There was no vasodilation to acetylcholine in either group, but there was a normal response to prostacyclin in NE-ARF. Smooth muscle necrosis was found in 46% of resistance arterial vessels in RAC- but in only 8% of NE-ARF (p<. 001). When mean arterial pressure was reduced to 90 mm Hg for 4 h at 1 week, recurrent azotemia and fresh ischemic injury were noted in NE- but not RAC-ARF. It is concluded that different models of ischemic ARF induction result in dfferent patterns of abnormal postischemic vascular reactivity. Differences in vascular smooth muscle and endothelial injury are due to differences in initial ischemia or rates of postischemic reperfusion.

ISSN:0886-022X    

DOI:10.3109/08860229209106634

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Glutathione is an important intracellular antioxidant in virtually all tissues, including the kidney. In the kidney, it has a rapid turnover in tubule cells and likely plays a role in any oxidant-related events which contribute to the tubule cell injury which occurs during acute renal failure. It was surprising, therefore, to find that the component amino acid, glycine, rather than glutathione itself, most strongly modulated the sensitivity of tubules cells to a variery of insults in several in vitro systems where rhese processes can be studied most directly. lhis paper reviews available evidence concerning the nature of both glutathione and glycine efects, their expression in vivo in in vitro, and their implications for understandng acute renal failure.

ISSN:0886-022X    

DOI:10.3109/08860229209106635

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Oxygen tension within the renal parenchyma is influenced by two factors: metabolic demand and oxygen supply. There are three regions within the kidney in which there is an anatomical basis for limited oxygen availability. The first is the inner stripe where oxygen dfision between arterial and venous vasa recta reduces PO,. The other two are the outer stripe and medullary rays which are fed by 02-poor blood from venous vasa recta. The balance between oxygen demand and supply is most critical in the inner stripe where the po2 is most influenced by transport activity. In contrasr, altering transport activities in the outer stripe will not change the prevalence of hypmic S3 injury but will alter its type (i.e., cell fragmentation related to high GFR and increased workload versus cell edema related to low GFR and minimal workload). The effect of transport activity on medullary ray PO2, has not been well defined. Using sensitive oxygen microelectrodes, cortical PO2, (52±2 mm Hg) in the rat was found to be higher than medullary PO2 (21±2 mm Hg, P<0.001). How are these observations reflected in current models of acute renal failure? The ischemia-reflow model affects proximal tubules with a predilection for S3 (located within the outer stripe of medulla) afier short-term ischemia. With hyperfiltration (induced by glycine or renal hypertrophy) and the pursuant increase in transport related 02 demand, hypmic mTAL inner stripe injury becomes prominent. Renal parenchymal hypertrophy exaggerates injury in the contrast nephropathy model, in which mTAL inner stripe injury is a predominant feature and medullary PO, is very low. In this model, with the additional stimulus of hyperjlltration induced by amino acid infusion, metabolic 02 demand rises and the mTAL inner stripe injury markedly increases. Myoglobin-induced renal failure is another example of hypoxia-related renal injury, but other factors may be important as well. Thus, alterations in the balance between oxygen supply and demand in certain regions of the kidney may be crucial in the pathogenesis of various models of acute renal failure.

ISSN:0886-022X    

DOI:10.3109/08860229209106636

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Studies in heart, liver, and kidney have provided evidence that calcium is an important factor in cell injury. Calcium channel blockers are used with increasing frequency in ischemic and toxic renal failure. In this review the available data on the effects of calcium channel blockers in animal models of ischemic renal failure are presented and possible mechanisms of protective actions are discussed.

ISSN:0886-022X    

DOI:10.3109/08860229209106637

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

ISSN:0886-022X    

DOI:10.3109/08860229209106638

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Severity of renal injury and recovery offunction in acute renal failure (ARF) are strongly related not only to the magnitude and nature of ARF insult but also to numerous factors in the host which govern renal susceptibility to the insult and repair of renal lesion. Prior ARF aflords resistance to a rechallenge with the same or different ARF insult. The mechanism for this acquired resistance to ARF have not been well established, but suggested mechanisms include (a) increased resistance of regenerated tubular epithelial cells to a rechallenge, (b) glomenrlar refractoriness to vasoactive substances, (c) failure of damaged kidney to concentrate the toxic substance, (d) enhanced antioxidant enzyme activity in glomeruli, and (e) increased Na+-K+-A Pase activity in regenerated tubular epithelial cells. Controversy still exists regarding roles of these factors in the resktance to renal failure. Functional and morphologic recovery of postischemic kidney is enhanced by antecedent unilateral nephrectomy but delayed in the presence of the contralateral kidney. The mechanisms for the effect of uninephrectomy remain unsettled. Recent studies suggest contributions of changes in preglomeruhr vascular resktance; alterations in the environment which follow ischemia to all functioning wcretory renal tissues; and altered production and release of vasoactive substances such as angiotensin, endothelin, thromboxane, and atrial natriuretic peptide.

ISSN:0886-022X    

DOI:10.3109/08860229209106639

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

ISSN:0886-022X    

DOI:10.3109/08860229209106640

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Although some humoral and neural factors have been implicated in the persistent vasoconstriction characterizing many forms of acute renal failure, the mechanisms for this abnonnal vascular function have remained largely unresolved. Several factors previously postulated to have a role in acute renal failure have been shown to enhance endothelin (Et) production or gene expression. We studied the potential pathophysiologic role for Et in several models of acute renal failure, including postischemia, endotoxin, and cyclosponne (Cy) nephrotoxicity. We have found that, in vivo, Cy (and also endotoxin) elevates circulating Et. We further showed that antagonizing Et s action with Et antibody ameliorates renal vasoconstriction following renal ischemia, Cy, and endotoxin administrntion. Additionally, our studies showed that even afer circulating levels of Et decrease following Cy), there is upregulation in Et receptors in the kidneys. Overall, endothelin appears to feature prominently in the pathophysiologic processes occum'ng during seveml forms of acute renal failure.

ISSN:0886-022X    

DOI:10.3109/08860229209106641

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor