Blunted Indomethacin-Induced Downregulation of Aquaporins by Nitric Oxide Synthesis Inhibition in Rats

The present study was aimed to determine whether nitric oxide (NO) plays a role in the regulation of aquaporin (AQP) channels in the kidney. Male Brattleboro rats (250~300 g body weight) were used. The experimental group was treated with N(G)-nitro-L-arginine methyl ester (L-NAME, 100 mg/L drinking water) for 1 week, and cotreated with indomethacin (5 mg/kg, twice a day, i.p.) for the last two days. Control groups were treated with either L-NAME for 1 week, indomethacin for 2 days, or without any drug treatment. The abundance of AQP1, AQP2 and AQP3 proteins in the kidney was determined by Western blot analysis. Indomethacin downregulated AQP channels, whereas L-NAME by itself showed no significant effects on them. The indomethacin-induced downregulation of AQP2 and AQP3 was significantly blunted in L-NAME-treated rats, while that of AQP1 was not affected. These results suggest that endogenous NO, when stimulated, may downregulate AQP channels that are specifically regulated by AVP/cAMP pathway in the kidney.

The role of the distal nephron in the regulation of acid-base equilibrium by the kidney

The present paper reviews mechanisms by which the kidney controls systemic acid-base balance, with emphasis on the role of the distal nephron, and particularly of the cortical distal tubule. These mechanisms are essentially based on H-ion transport along the whole nephron. In proximal tubule cells, approximately 80 of H-ion secretion is mediated by Na+/H+ exchange, and 20 by H(+)-ATPase. In the distal nephron, acid-base transport mechanisms are located mainly in intercalated cells. H-ion secretion is effected by vacuolar H(+)-ATPase in alpha-intercalated cells and, in K-depleted animals, also by the gastric type H/K ATPase. In animals in alkalosis, beta-intercalated cells secrete bicarbonate by an apical Cl-/HCO3- exchanger, while a basolateral H-ATPase transfers H-ions into the interstitium. In cortical distal tubule, these mechanisms have been shown to be present in the intercalated cells of the connecting segment and of the initial collecting duct (the late distal tubule of micropuncture experiments). In the convoluted distal tubule (early distal tubule), most H-ion secretion occurs by means of the Na+/H+ exchanger. These data show that the distal nephron, including the cortical distal tubule, is a nephron segment responsible for a sizeable portion of bicarbonate reabsorption and titratable acid generation, as well as for bicarbonate secretion under appropriate metabolic conditions, being therefore the site of fine regulation of renal mechanisms that maintain acid-base homeostasis.

Interaçäo do hormônio antidiurético e das prostaglandinas na progressäo da insuficiência renal experimental / Interaction of antidiuretic hormone and prostaglandins in the progression of experimental renal failure

Utilizamos ratos com diabetes insipidus congênito (Brattlelboro), submetidos a reduçäo de 5/6 da massa renal total, a fim de avaliarmos a participaçäo do hormônio antidiurético (HAD) na funçäo renal do rim remanescente. Verificamos que, na ausência do HAD, näo ocorre hiperfiltraçäo adaptativa, ou seja, a filtraçäo glomerular global se manteve reduzida e a filtraçäo glomerular por néfron foi normal. Esses resultados säo bastante distintos do que ocorre com outras raças de ratos, submetidos a similar reduçäo da massa renal. Paralelamente, avaliamos a participaçäo das prostaglandinas (PGs) neste modêlo, através da inibiçäo deste sistema com indometacina. Também verificamos que na ausência do HAD o bloqueio agudo das PGs näo ocasionou alteraçäo na funçäo renal nestes animais. Diferencialmente, em ratos com HAD (Munich-Wistar, a inhibiçäo das PGs na IRC ocasiona diminuiçäo significativa da hiperfiltraçäo glomerular global e por néfron

Caracterizaçäo do rato com diabetes insípido hereditário - Brattleboro - criado no Brasil / Characterization of the Brattleboro rat bred in Brazil

O rato Brattleboro é um modelo experimental de diabetes insípido, sendo que em ratos homozigotos (di/di) há ausência total do hormônio antidiurético (ADH), enquanto que em heterozigotos (di/+) ocorre apenas a produçäo de 50%. Neste trabalho, os autores comparam a qualidade da colônia durante três anos e determinam algumas variáveis fisiológicas em ratos di/di e di/+. Os resultados sugerem que a boa adaptaçäo dos animais no primeiro ano näo significou o sucesso do programa decriaçäo, uma vez que o número de di/di obtido näo foi satisfatório, indicando possíveis acasalamentos inadequados resultantes de falhas no método de classificaçäo. Ratos di/di apresentaram baixo peso corporal e elevado consumo de água e durese em comparaçäo aos di/+. O Na plasmático e sua excreçäo urinária foram maiores em di/di, enquanto que näo observamos diferenças, em média, no peso do rim, hematócrito e proteínas plasmáticas. Ratos di/di apresentaram menor pressäo arterial média e resistência vascular renal, indicando ausência do efeito vasoconstrictor do ADH. Portanto, sugerimos que, apesar das dificuldades na produçäo e manutençäo, esse animal é excelente modelo experimental para o estudo do ADH em várias situaçöes fisiológicas e fisiopatológicas

Release of alpha-MSH from the in vitro superfused neuro-intermediate lobe of the pituitary of the rat by antidiuretic hormone.

The effect of antidiuretic hormone (ADH) on the release of immunoreactive alpha-melanocyte stimulating hormone (alpha-MSH) from the superfused neurointermediate lobe of the pituitary of the normal Wistar and Brattleboro (diabetes insipidus) rat was studied in vitro. In control experiments, there was usually an initial peak, after which alpha-MSH release fell exponentially over the course of the perfusion. Following the addition of ADH, the levels of alpha-MSH in the superfusate showed a significant rise. It is suggested that ADH is normally involved in the secretion of alpha-MSH by the pars intermedia of the rat, especially in response to osmotic stimuli.