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Abstract: Pseudohypoaldosteronism (PHA) comprises a diverse group of rare diseases characterized by sodium and potassium imbalances incorrectly attributed to a defect in aldosterone production. Two different forms of PHA have been described, type I (PHAI) and type II (PHAII). PHAI has been subclassified into renal and systemic. Given the rarity and heterogeneity of this group of disorders we report three patients who carry PHA and a brief revision of current literature focused on the comparative analysis of PHAI and PHAII. Cases 1 and 2 presented with hyponatremia, hyperkalemia, metabolic acidosis and elevated plasma aldosterone and plasma renin activity in the neonatal period. Sequence analysis of the NRC2 gene demonstrated a novel heterozygous c.403C>T mutation in case 1 and a complete deletion in case 2, confirming the diagnosis of renal PHAI. Case 3 was a 4-year-old with hypertension, hyperkalemia, metabolic acidosis, normal plasma aldosterone and decreased plasma renin activity. Sequence analysis of the CUL3 gene demonstrated a previously unreported heterozygous c.1377+2T>3 mutation, confirming the diagnosis of PHAII-E. We highlight the importance of the determination of plasma aldosterone and plasma renin activity in the context of persistent sodium and potassium imbalances in children. [ABSTRACT FROM AUTHOR]

Abstract: We have previously shown that centrally injected melittin, a phospholipase A2 (PLA2) activator, increases blood pressure and decreases heart rate in the normotensive conscious rats. In the current study we aimed to determine the cardiovascular effects of melittin in hemorrhaged hypotensive rats and to investigate the mediation of peripheral adrenergic, vasopressinergic and renin angiotensin system in the pressor effect of centrally administrated melittin in both normotensive and hypotensive conditions. Acute hypotensive hemorrhage was performed by withdrawing a total volume of 2.2ml of blood/100g body weight over a period of 10min. Melittin was injected intracerebroventricularly (i.c.v.) at the doses of 1.5μg, 3.0μg or 6.0μg after the stabilization period of hemorrhage procedure. We also repeated previous experiments by injecting melittin (1.5μg, 3.0μg or 6.0μg; i.c.v.) to the normotensive animals. Melittin caused dose- and time-dependent increases in mean arterial pressure (MAP) in normal and hypotensive conditions and decreases in heart rate (HR) in normotensive conscious animals. In hypotensive rats, melittin injected at the dose of 6.0μg completely restored the decrease in blood pressure. Plasma adrenaline, noradrenaline, vasopressin levels and renin activity increased after melittin (3.0μg; i.c.v) administration in normal conditions. Hemorrhage, itself, produced an increase in these plasma hormone levels and melittin (3.0μg; i.c.v.) caused additional increases in plasma adrenaline, noradrenaline, vasopressin levels and renin activity in hypotensive conditions. Intravenous pretreatments of rats with prazosin (0.5mg/kg), an α1 adrenoceptor antagonist, [β-mercapto-β,β-cyclopentamethylenepropionyl1, O-Me-Tyr2-Arg8]-vasopressin (10μg/kg), a vasopressin V1 receptor antagonist, or saralasin (250μg/kg), an angiotensin II receptor antagonist, partially blocked the pressor response to melittin (3.0μg; i.c.v.) in both normotensive and hypotensive conditions. Besides, the combined administration of these three antagonists before melittin completely abolished the pressor responses to drug in both conditions. Results show that centrally administered melittin, a PLA2 activator, increases blood pressure and reverses hypotension in hemorrhagic shock. The increases in plasma adrenaline, noradrenaline, vasopressin levels and renin activity mediate the pressor responses to melittin in normal and hypotensive conditions. [Copyright &y& Elsevier]

Abstract: Background: Female humans and rodents are relatively protected against the development of hypertension and renal disease. Whether this protection is modified during insulin resistance and obesity, however, is not known. Objective: Because renal sodium reabsorption has a central role in determining blood pressure, we hypothesized that lean female rats would bave reduced renal expression, activity, and urinary excretion of 8 major sodium transporters/channels. Methods: Lean and obese, male and female Zucker rats (n = 4–8 per group) were fed progressively higher levels of dietary NaCl over a period of 54 days. Urinary excretion of renal sodium transport proteins was determined for 3 different dietary levels (0.04%, 0.4%, and 4%) of NaCl. With the high-NaCl diet, natriuretic responses to benzamil, furosemide, and thiazide were used as in vivo markers for activity of the epithelial sodium channel (ENaC), the bumetanide-sensitive Na-K-2C1 cotransporter (NKCC2), and the thiazide-sensitive NaCl cotransporter (NCC), respectively. Results: Female rats (of both body types) had lower plasma renin activity and insulin levels than their male counterparts. Likewise, immunoblotting revealed female rats had increased whole kidney abundance of NCC and of the α, β, and γ subunits of ENaC, as well as decreased abundance of the type 3 sodium hydrogen exchanger (NHE3), type 2 sodium phosphate cotransporter (NaPi-2), and α-1 sodium-potassium-adenosine triphosphatase (Na-K-ATPase), compared with males. Obese rats had reduced levels of NKCC2, NHE3, and γ-ENaC, but higher levels of NaPi-2 and NCC. Urine excretion of sodium transporters in lean female rats was nearly undetectable, whereas obese rats of both sexes excreted markedly more NKCC2 and NCC, which agreed with greater natriuretic responses to thiazide and furosemide. Conclusions: Obese female rats are similar to lean female rats with regard to the sex-distinct pattern of renal sodium transporters. However, obese female rats are more like obese male rats with regard to increased natriuretic response tofurosemide and thiazide, and to urine excretion of several transporters including NCC. Our results suggest that, with obesity, there is some loss of the protective female advantage. [Copyright &y& Elsevier]