Inhibition of Dehydration-Induced Water Intake by Glucocorticoids Is Associated with Activation of Hypothalamic Natriuretic Peptide Receptor-A in Rat

Atrial natriuretic peptide (ANP) provides a potent defense mechanism against volume overload in mammals. Its primary receptor, natriuretic peptide receptor-A (NPR-A), is localized mostly in the kidney, but also is found in hypothalamic areas involved in body fluid volume regulation. Acute glucocorticoid administration produces potent diuresis and natriuresis, possibly by acting in the renal natriuretic peptide system. However, chronic glucocorticoid administration attenuates renal water and sodium excretion. The precise mechanism underlying this paradoxical phenomenon is unclear. We assume that chronic glucocorticoid administration may activate natriuretic peptide system in hypothalamus, and cause volume depletion by inhibiting dehydration-induced water intake. Volume depletion, in turn, compromises renal water excretion. To test this postulation, we determined the effect of dexamethasone on dehydration-induced water intake and assessed the expression of NPR-A in the hypothalamus. The rats were deprived of water for 24 hours to have dehydrated status. Prior to free access to water, the water-deprived rats were pretreated with dexamethasone or vehicle. Urinary volume and water intake were monitored. We found that dexamethasone pretreatment not only produced potent diuresis, but dramatically inhibited the dehydration-induced water intake. Western blotting analysis showed the expression of NPR-A in the hypothalamus was dramatically upregulated by dexamethasone. Consequently, cyclic guanosine monophosphate (the second messenger for the ANP) content in the hypothalamus was remarkably increased. The inhibitory effect of dexamethasone on water intake presented in a time- and dose-dependent manner, which emerged at least after 18-hour dexamethasone pretreatment. This effect was glucocorticoid receptor (GR) mediated and was abolished by GR antagonist RU486. These results indicated a possible physiologic role for glucocorticoids in the hypothalamic control of water intake and revealed that the glucocorticoids can act centrally, as well as peripherally, to assist in the normalization of extracellular fluid volume

Anthropogenic–biogenic interaction amplifies warming from emission reduction over the southeastern US

A decline of surface biogenic secondary organic aerosols through the mediation of reduced anthropogenic aerosols has been recognized as an air quality co-benefit of anthropogenic emission control over the southeastern US. However, the climate impacts of this anthropogenic–biogenic interaction remain poorly understood. Here, we identified a substantial decline of summertime aerosol loading aloft over the southeastern US in recent decades through the interaction, which leads to a stronger decline in column-integrated aerosol optical depth and a greater increase in radiative fluxes over the southeastern than northeastern US, different from trends of anthropogenic emissions and near-surface aerosol loading. The anthropogenic–biogenic interaction is shown to explain more than 60% of the coherent increasing trend of 5.3 Wm ^−2 decade ^−1 in clear-sky surface downward radiative fluxes. We show that current climate models fail to represent this interaction. The interaction is further projected to amplify the positive radiative forcing from emission control by 42.3% regionally over the southeastern US and globally by 5.4% in 2050 under RCP4.5 compared to 2005. This amplification effect implies greater challenges to achieving the Paris Agreement temperature targets with continuous emission control in future

The effect of 24-hour Dex pretreatment on urinary volume and water intake.

<p>[<b>A</b>] Effect of Dex pretreatment on urinary volume during 24-hour pretreatment period; *<0.01 compared with rats treated with vehicle. [<b>B</b>] Effect of Dex pretreatment on cumulative water intake during water-access period in the dehydrated rats; n = 10 for each group; data were analyzed by two-way repeated measures ANOVA; *<0.01 compared with rats treated with vehicle; # <0.01 compared with rats treated with low dose of Dex. [<b>C</b>] Effect of Dex pretreatment on urinary volume during water-access period.</p

The effect of 18-hour Dex pretreatment on urinary volume and water intake.

<p>[<b>A</b>] Effect of Dex pretreatment on urinary volume during 18-hour pretreatment period; *<0.01 compared with rats treated with vehicle. [<b>B</b>] Effect of Dex pretreatment on cumulative water intake during water-access period in the dehydrated rats; n = 10 for each group; data were analyzed by two-way repeated measures ANOVA; *<0.01 compared with rats treated with vehicle. [<b>C</b>] Effect of Dex pretreatment on urinary volume during water-access period; *<0.01 compared with rats treated with vehicle; # <0.01 compared with rats treated with low dose of Dex.</p

The effect of Dex pretreatment on plasma ANP and hypothalamic ANP content in the water-deprived rats.

<p>[<b>A</b>] Effect of 6-hour Dex pretreatment on plasma ANP levels in water-deprived rats; *<0.01 compared with rats treated with vehicle; # <0.01 compared with rats treated with low dose of Dex. [<b>B</b>] Effect of 24-hour Dex pretreatment on plasma ANP levels in water-deprived rats; *<0.01 compared with rats treated with vehicle; # <0.01 compared with rats treated with low dose of Dex. [<b>C</b>] Effect of 24-hour Dex pretreatment on hypothalamic ANP contents in water-deprived rats; n = 10 for each group.</p

The effect of Dex on hypothalamic NPR-A expression and cGMP content in the water-deprived rats.

<p>[<b>A</b>], [<b>B</b>] Effect of Dex pretreatment on hypothalamic NPR-A expression in the water-deprived rats. [<b>C</b>] Effect of Dex on hypothalamic cGMP content in the water-deprived rats. n = 8 for each group. *<0.05 compared with vehicle. [<b>D</b>], [<b>E</b>] NPR-A positive neurons visualized by immunofluorescence in the hypothalamus (white arrows denote increased NPR-A positive neurons) in the water-deprived rats. Abbreviations: RCh, retrochiasmatic nucleus; sox, Supraoptic decussation; 3V, third ventricle. [<b>F</b>] Schematic drawing of a coronal section of the rat brain (from ref. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0015607#pone.0015607-Paxinos1" target="_blank">[37]</a>) at the level shown in [D] and [E]. The area defined by the square is shown in [D] and [E].</p

The effect of 6-hour Dex pretreatment on urinary volume and water intake.

<p>[<b>A</b>] Effect of Dex pretreatment on urinary volume during 6-hour pretreatment period; *<0.01 compared with rats treated with vehicle. [<b>B</b>] Effect of Dex pretreatment on cumulative water intake during water-access period in the dehydrated rats; n = 10 for each group; data were analyzed by two-way repeated measures ANOVA. [<b>C</b>] Effect of Dex pretreatment on urinary volume during water-access period; *<0.01 compared with rats treated with vehicle; # <0.01 compared with rats treated with low dose of Dex.</p

Potent volume depleting effect by Dex in rats given ad libitum access to food and water.

<p>[<b>A</b>] Effect of Dex on cumulative urinary volume; n = 10 for each group; * <0.01 compared with rats treated with vehicle; # <0.01 compared with rats treated with low dose of Dex. [<b>B</b>] Effect of Dex on cumulative urinary sodium; * <0.01 compared with rats treated with vehicle; # <0.01 compared with rats treated with low dose of Dex. [<b>C</b>] Effect of Dex on cumulative water intake. [<b>D</b>] Effect of Dex on food intake. [<b>E</b>] Effect of Dex on change from baseline in body weight; * <0.01 compared with rats treated with vehicle; # <0.01 compared with rats treated with low dose of Dex.</p

Reversal of the effects of Dex on body fluid metabolism by RU486 in the water-deprived rats.

<p>[<b>A</b>] RU486 reversed the effect of Dex on urinary volume in the water-deprived rats. #<0.01 compared with rats treated with vehicle. [<b>B</b>] RU486 reversed the effect of Dex on water intake over 12-hour water-access period in the dehydrated rats; n = 10 for each group; data were analyzed by two-way repeated measures ANOVA; # <0.01 compared with rats treated with vehicle. [<b>C</b>], [<b>D</b>], [<b>E</b>] RU486 reversed the effect of Dex on hypothalamic NPR-A expression and cGMP production in the water-deprived rats; n = 8 for each group; *<0.05 compared with rats treated with vehicle; # <0.01 compared with rats treated with vehicle. [<b>F</b>] Rabbit anit-hANP antiserum blocked the inhibitory effects of Dex on water intake in water-deprived rats; n = 5–6 in each group; vehicle  =  normal rabbit serum; data were analyzed by two-way repeated measures ANOVA; # <0.01 compared with rats treated with vehicle.</p