American journal of physiology. Renal physiology
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Am. J. Physiol. Renal Physiol. · Sep 2002
Mineralocorticoid regulation of cyclooxygenase-2 expression in rat renal medulla.
The renal inner medulla and its distal one-third, the papilla, are major sites of prostanoid synthesis involved in water and electrolyte homeostasis. These sites contain variable levels of cyclooxygenase (COX)-2, a key prostaglandin synthase enzyme that is sensitive to adrenal steroids. Immunoreactive renal medullary COX-2, restricted to interstitial cells in control adult rats, shows a gradient of intense staining at the tip of the papilla that gradually diminishes to undetectable levels in the proximal inner medulla. ⋯ DOCA treatment of mouse renal medullary interstitial cells in culture had no effect, but increased tonicity of the culture medium with NaCl caused strong upregulation of COX-2. Urea, a permeant molecule, had no effect. Together, these results suggest that mineralocorticoids lead to upregulation of COX-2 in rat renal medulla by indirect pathways, probably involving induced electrolyte hypertonicity in the interstitial fluid.
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Newborn rats are not capable of producing concentrated urine. With development of the concentrating system and a hypertonic medullary interstitium, intracellular osmolytes, such as sorbitol, accumulate in the renal medulla. Sorbitol is produced from glucose in a reaction catalyzed by aldose reductase (AR). ⋯ The expression of AR in both the ATL and the IMCD gradually increased during kidney development. We conclude that AR expression in the inner medulla coincides with the increase in medullary tonicity that is known to occur during the first 3 wk after birth. On the basis of the observation that only AR-negative cells were deleted by apoptosis in the differentiating ATL, we propose that AR may protect ATL cells against apoptosis.
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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.