American journal of physiology. Renal physiology
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Am. J. Physiol. Renal Physiol. · Sep 2002
Protective effect of renal denervation on normotensive endotoxemia-induced acute renal failure in mice.
Acute renal failure (ARF) contributes substantially to the high morbidity and mortality observed during endotoxemia. We hypothesized that selective blockade of the renal nerves would be protective against ARF during the early (16 h) stage of endotoxemia [5 mg lipopolysaccharide (LPS)/kg ip in mice]. At 16 h after LPS, there was no change in mean arterial pressure, but plasma epinephrine (4,604 +/- 719 vs. 490 +/- 152 pg/ml, P < 0.001), norepinephrine (2,176 +/- 306 vs. 1,224 +/- 218 pg/ml, P < 0.05), and plasma renin activity (40 +/- 5 vs. 27 +/- 2 ng x ml(-1) x h(-1), P < 0.05) were higher in the LPS-treated vs. control mice. ⋯ The decrement in glomerular filtration rate during endotoxemia was significantly attenuated in mice with denervated kidneys (32 vs. 79%). Moreover, there was no change in renal blood flow during endotoxemia in mice with renal denervation. The present results therefore demonstrate a protective role of renal denervation during normotensive endotoxemia-related ARF in mice, an effect that may be, at least in part, due to a diminished activation of the renin-angiotensin system.
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Am. J. Physiol. Renal Physiol. · Jun 2002
Endothelial dysfunction in ischemic acute renal failure: rescue by transplanted endothelial cells.
There is accumulating circumstantial evidence suggesting that endothelial cell dysfunction contributes to the "no-reflow" phenomenon in postischemic kidneys. Here, we demonstrated the vulnerability of in vitro, ex vivo, and in vivo endothelial cells exposed to pathophysiologically relevant insults, such as oxidative and nitrosative stress or ischemia. All of these stimuli compromised the integrity of the endothelial lining. ⋯ In an attempt to ameliorate the hemodynamic consequences of lost endothelial integrity, we transplanted endothelial cells or surrogate cells expressing endothelial nitric oxide synthase into rats subjected to renal artery clamping. Implantation of endothelial cells or their surrogates expressing functional endothelial nitric oxide synthase in the renal microvasculature resulted in a dramatic functional protection of ischemic kidneys. These observations strongly suggest that endothelial cell dysfunction is the primary cause of the no-reflow phenomenon, which, when ameliorated, results in prevention of renal injury seen in acute renal failure.
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We utilized immunofluorescent immunolabeling of renal tissue sections to identify and count tubules at specified depths of the rat renal inner medulla. We used primary antibodies to aquaporin-1 (AQP1; labeling thin descending limbs), aquaporin-2 (AQP2; labeling inner medullary collecting ducts), the rat kidney-specific chloride channel (ClC-K1; labeling thin ascending limbs), and von Willebrand factor (labeling descending vasa recta). Secondary antibodies conjugated to different fluorophores were used, giving up to a three-color display. ⋯ In addition, thin limbs were found to label with antibodies to ClC-K1 on both sides of their hairpin turns. We conclude that the descending thin limbs shift from expressing AQP1 to expressing ClC-K1 some distance before the point where they turn and begin to ascend. Mathematical models can use our quantitative data to explore implications for the urine-concentrating mechanism.
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Am. J. Physiol. Renal Physiol. · Feb 2002
Losartan treatment normalizes renal sodium and water handling in rats with mild congestive heart failure.
This study was designed to examine the effect of losartan treatment on renal tubular function in rats with mild congestive heart failure (CHF) induced by ligation of the left anterior descending artery. In rats with CHF, there was a significant decrease in daily sodium excretion, which caused sodium retention relative to control rats. Renal function studies revealed that glomerular filtration rate and proximal tubular sodium handling were normal. ⋯ Losartan treatment normalized expression of NKCC2 and decreased expression of the vasopressin-regulated water channel aquaporin-2. This was associated with normalization of daily sodium excretion and normalization of the aquaretic response to V(2)-receptor blockade. Together, these results indicate that, in rats with CHF, losartan treatment inhibits increased sodium reabsorption through NKCC2 in the thick ascending limb of Henle's loop and water reabsorption through aquaporin-2 in the collecting ducts, which may be involved in improving renal function in losartan-treated CHF rats.
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Am. J. Physiol. Renal Physiol. · Feb 2002
Blood flow-dependent changes in renal interstitial guanosine 3',5'-cyclic monophosphate in rabbits.
We examined responses of renal interstitial guanosine 3',5'-cyclic monophosphate (cGMP) to changes in renal perfusion pressure (RPP) within and below the range of renal blood flow (RBF) autoregulation. A microdialysis method was used to monitor renal cortical and medullary interstitial cGMP levels in anesthetized rabbits. RPP was reduced in two steps: from ambient pressure (89 +/- 3 mmHg) to 70 +/- 2 mmHg (step 1) and then to 48 +/- 3 mmHg (step 2). ⋯ During L-NAME treatment, renal interstitial concentrations of cGMP in the cortex and medulla were similarly not altered in step 1. However, L-NAME significantly attenuated cGMP responses to a reduction in RPP in step 2. These results indicate that acute changes in RBF result in alterations in nitric oxide-dependent renal interstitial cGMP levels, with differential effects in the medulla compared with the cortex.