Dietary salt with nitric oxide deficiency induces nocturnal polyuria in mice via hyperactivation of intrarenal angiotensin II-SPAK-NCC pathway

Abstract

Nocturnal polyuria is the most frequent cause of nocturia, a common disease associated with a compromised quality of life and increased mortality. Its pathogenesis is complex, and the detailed underlying mechanism remains unknown. Herein, we report that concomitant intake of a high-salt diet and reduced nitric oxide (NO) production achieved through Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) administration in mice resulted in nocturnal polyuria recapitulating the clinical features in humans. High salt intake under reduced NO production overactivated the angiotensin II-SPAK (STE20/SPS1-related proline–alanine-rich protein kinase)-NCC (sodium chloride co-transporter) pathway in the kidney, resulting in the insufficient excretion of sodium during the day and its excessive excretion at night. Excessive Na excretion at night in turn leads to nocturnal polyuria due to osmotic diuresis. Our study identified a central role for the intrarenal angiotensin II-SPAK-NCC pathway in the pathophysiology of nocturnal polyuria, highlighting its potential as a promising therapeutic target.

Hyperchloremia and Hypernatremia Decreased Microglial and Neuronal Survival during Oxygen–Glucose Deprivation/Reperfusion

“…The freely diffusible gaseous compound NO is an important messenger in many organ systems, particularly the CNS [ 56 ]. Earlier studies also suggested high salt intake can reduce NO production in different cell types [ 31 , 57 ]. However, exposure to a 3:1 and 1:1 combination of NaCl and CH 3 COONa-treated microglial media in neuronal cells showed an increase in nitric oxide (NO) production in neuronal cells.…”

Electrolyte Disorders in Mitochondrial Cytopathies: A Systematic Review

“…For example, a deficiency of nitric oxide can lead to either sodium retention or sodium wasting, possibly depending on the specific tubular location and timing (nitric oxide has a short half-life). [107][108][109] Deficiency of nitric oxide is a hallmark of some mitochondrial diseases, 110 and it is likely to be present in other mitochondrial diseases as well because of the production of reactive oxygen species. 107 Hypothetically, different mitochondrial defects might have different effects on the production of reactive oxygen species and nitric oxide, depending on the cell type and its unique metabolic wiring, and thereby differ in the effect on electrolyte reabsorption.…”

Emerging structural and pathological analyses on the erectile organ, corpus cavernous containing sinusoids

“…They contribute to understanding of the mechanisms for erection such as the signal cascade of nitric oxide synthase (NOS)‐cGMP axis 8 . Generally, recent urological research showed significant advances in the research field for NO signal and local neuronal regulation 9,10 . There are growing concerns about pathological mechanisms of ED and the effect of aging on the erectile structure including fibrosis and aberrant chondrogenesis 11,12 .…”

“…research field for NO signal and local neuronal regulation. 9,10 There are growing concerns about pathological mechanisms of ED and the effect of aging on the erectile structure including fibrosis and aberrant chondrogenesis. 11,12 However, analyses of such pathological changes inside the erectile system, the sinusoids has rarely been studied through only a few histological studies.…”