K + balance in mammals relies on regulated renal K + excretion matching unregulated fluctuating K + intake. Upon a K + rich meal, rapid and powerful K + excretion is needed. Renal K + secretion is stimulated by the increased tubular flow.We speculated that high K + intake acutely increases urinary flow to stimulate K + excretion.Methods: Mice were K + challenged through diets or gavage. Post K + loading urinary output, osmolarity, [K + ] u , [Na + ] u , plasma osmolarity, [copeptin] p , [K + ] p , and [Na + ] p were measured. To locate the mechanism of K + -induced diuresis in the glomerular/tubular system we measured creatinine excretion and assessed functional transport in isolated perfused TALs and CDs during an acute [K + ] bl switch from 3.6 to 6.5 mM. Molecular adaptations of transport proteins involved in water reabsorption were investigated by immunoblotting. Results:(1) Mice switched from a 1% to 2% K + diet increased diuresis within 12 hours and reciprocally reduced diuresis when switched from 1% to 0.01% K + diet. (2) A single K + gavage load, corresponding to 25%-50% of daily K + intake, induced 100% increase in diuresis within 30 minutes. This occurred despite augmented plasma osmolarity and AVP synthesis. (3) K + gavage did not change GFR.(4) In isolated perfused TALs, shifting [K + ] bl from 3.6 to 6.5 mM did not affect AVP-induced NaCl transport. (5) In sharp contrast, in isolated perfused CDs, shifting [K + ] bl from 3.6 to 6.5 mM markedly reduced CD AVP sensitivity, ie inhibited water absorption. Conclusion:Dietary K + loading induces a rapidly on-setting diuresis. The mechanism of K + -induced diuresis involves desensitization of the CD to AVP. K E Y W O R D Santi-diuretic hormone, direct K + effect, diuresis, K + homeostasis, urinary K + excretion | INTRODUCTIONIn 1928, the Canadian physician William L. T. Addison showed that K + rich diets reduce blood pressure, whereas Na + rich diets had the opposite effect. 1 Numerous randomized trials have since then shown that a diet enriched with K + is associated with protection against hypertension, cardiovascular disease, and overall mortality. 2 These effects are not completely understood but are most likely associated with functional and molecular adaptations in renal water and salt handling. 3
High levels of persistent organic pollutants (POPs) and heavy metals are found in Arctic populations. POP and heavy metals are linked to impaired cognitive development. This study examined associations between prenatal POP and metals exposure and problematic child behavior using the Strength and Difficulties Questionnaire (SDQ). POPs and metals were measured in 102 pregnant Greenlandic women. During follow-up at 3–5 years, parents answered an assisted questionnaire including children’s SDQ scores. Associations were analyzed using linear and logistic regression analyses and adjusted for maternal plasma cotinine, educational level and age at delivery. In the adjusted analyses, the medium tertile of hexachlorobenzene (β = 3.06, p = 0.010), β-hexachlorocyclohexane (β = 3.58, p = 0.004) and trans-nonachlor (β = 2.06, p = 0.082) were positively associated with SDQ scores. The continuous cis-nonachlor (OR = 1.09, p = 0.079), dichloro-diphenyl-dichloroethylene (OR = 1.01, p = 0.077), trans-nonachlor (OR = 1.01, p = 0.091), and sum Organochlorine-Pesticides (OR = 1.00, p = 0.094) were positively associated with abnormal SDQ score and the continuous mirex (OR = 1.28, p = 0.096), oxychlordane (OR = 1.04, p = 0.066), and trans-nonachlor (OR = 1.02, p = 0.071) with abnormal hyperactivity score. We found no consistent evidence of associations between polychlorinated biphenyls, perfluoroalkylated substances and heavy metals and problematic behavior. Prenatal organochlorine pesticide exposure associated significantly with problematic behavior in 3–5 year old children.
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