No abstract

Pendrin (encoded by Pds, Slc26a4) is a Cl−/HCO3− exchanger expressed in the apical regions of type B and non-A, non-B intercalated cells of kidney and mediates renal Cl− absorption, particularly when upregulated. Aldosterone increases blood pressure by increasing absorption of both Na+ and Cl− through increased protein abundance and function of Na+ transporters, such as the epithelial Na+ channel (ENaC) and the Na+-Cl− cotransporter (NCC), as well as Cl− transporters, such as pendrin. Because aldosterone analogs do not increase blood pressure in Slc26a4−/− mice, we asked whether Na+ excretion and Na+ transporter protein abundance are altered in kidneys from these mutant mice. Thus wild-type and Slc26a4-null mice were given a NaCl-replete, a NaCl-restricted, or NaCl-replete diet and aldosterone or aldosterone analogs. Abundance of the major renal Na+ transporters was examined with immunoblots and immunohistochemistry. Slc26a4-null mice showed an impaired ability to conserve Na+ during dietary NaCl restriction. Under treatment conditions in which circulating aldosterone is increased, α-, β-, and 85-kDa γ-ENaC subunit protein abundances were reduced 15–35%, whereas abundance of the 70-kDa fragment of γ-ENaC was reduced ∼70% in Slc26a4-null relative to wild-type mice. Moreover, ENaC-dependent changes in transepithelial voltage were much lower in cortical collecting ducts from Slc26a4-null than from wild-type mice. Thus, in kidney, ENaC protein abundance and function are modulated by pendrin or through a pendrin-dependent downstream event. The reduced ENaC protein abundance and function observed in Slc26a4-null mice contribute to their lower blood pressure and reduced ability to conserve Na+ during NaCl restriction.

We hypothesized that neuronal mtrtc oxide synthase and cyclooxygenase-2, which both exist m the renal cortex, predommantly m the macula densa, play a role m the control of renal renm tissue content We studied the possible role of neuronal mtrrc oxide synthase m regulating renal renm content by using mice m which the neuronal nitric oxide synthase gene has been disrupted (nNOS -/-) compared with its two progemtor strains, the 129/SvEv and the C57BU6, to determine if the absence of neuronal mtrrc oxide synthase would result m decreased renal renm content or blunt the increase observed durmg low sodium intake. Renal remn content from cortical shces was determined m adult mice from all three strams maintained on a normal sodium diet Renal remn content was sigmficantly reduced m the nNOS -/-mice compared with the 129/SvEv and the C57BW6 mice (3 11 t0 23 versus 5 66+0 50 and 7 552 1 17 pg angrotensm Vmg dry weight, respectively, P< 005), suggestmg that neuronal nitric oxide synthase may stimulate renal renm content under basal condmons Neither selectrve pharmacologtcal mhlbition of neuronal mtrm oxide synthase using 7-mtromdazole or disruption of the neuronal nitric oxide synthase gene affected the increase m renal renm content observed during dietary sodium restriction The influence of cyclooxygenase-2 on renal renm content through a macula densa-mediated pathway was studied using a selecttve cyclooxygenase-2 Inhibitor, NS398, m 129/SvEv mace A low-sodium diet increased renal renm content from 6.97tO 52 to 11 5920 79 pg angrotensm Umg dry weight (P< 005), but thus increase was blocked by NS398 In addition, treatment with NS398 reduced renm mRNA m response to a low-sodium diet Thus, increased renal renm content m response to dietary sodmm restriction appears to require the mduction of cyclooxygenase-2, while neuronal nitric oxide synthase appears to affect basal but not stimulated renal renm content (Hypertenszon. 1997;29[part 2]:297-302.) Key Words l renm l cyclooxygenase l nitric oxide l mace T he mechanism by which a decreased sodmm chloride delivery to the macula densa IS sensed, resulting m increased renm secretion by the JUXtaglomerular cells, remains unknown. However, since humoral factors are known to affect rerun, attentton has focused on NO, which IS localized m a prime position to affect remn secretion and which has been imphcated m renm regulation by both m viva and m vitro studies.l-4 The enzyme NOS acts on its substrate L-argmme to produce NO It exists in three known isoforms that are discreetly localized throughout the nephron Briggs et a15 demonstrated that the macula densa is rich m nNOS, whereas nNOS does not appear to be expressed m the glomerulus, mesangium, or juxtaglomerular cells. In contrast, eNOS is expressed in the glomerulus and blood vessels 6 Smgh et a17 have also shown that the activity of nNOS m the macula densa is increased by a low-salt diet, whereas it does not affect eNOS. Therefore, NO produced m the macula densa could exert an effect directly on the adJoining juxtaglomerul...

We used a new radiopharmaceutical agent, [131I]meta-iodobenzylguanidine ([131I]MIBG), to produce scintigraphic images of pheochromocytomas in eight patients. One day or more after injection, the only normal organ that displayed distinct concentrations of radioactivity was the urinary bladder. The [131I]MIBG was probably concentrated in adrenergic vesicles; in tissues where vesicles are numerous, such as pheochromocytomas, the radionuclide was retained for days. The spectrum of pheochromocytomas shown the scintigrams was broad: intra-adrenal and extraadrenal in location, benign and malignant in character, 0.2 to 65 g in weight, and with different hormone patterns in secretion. Tumors in four patients were not detected by computed tomography. In one patient, reoperation was undertaken only because the scintigram located the extra-adrenal tumors and thereby directed the surgeon's exploration. The method offers hope of safe and reliable localization of pheochromocytomas in their many guises.