Activation of ENaC by AVP contributes to the urinary concentrating mechanism and dilution of plasma

Abstract

Arginine vasopressin (AVP) activates the epithelial Na(+) channel (ENaC). The physiological significance of this activation is unknown. The present study tested if activation of ENaC contributes to AVP-sensitive urinary concentration. Consumption of a 3% NaCl solution induced hypernatremia and plasma hypertonicity in mice. Plasma AVP concentration and urine osmolality increased in hypernatremic mice in an attempt to compensate for increases in plasma tonicity. ENaC activity was elevated in mice that consumed 3% NaCl solution compared with mice that consumed a diet enriched in Na(+) with ad libitum tap water; the latter diet does not cause hypernatremia. To determine whether the increase in ENaC activity in mice that consumed 3% NaCl solution served to compensate for hypernatremia, mice were treated with the ENaC inhibitor benzamil. Coadministration of benzamil with 3% NaCl solution decreased urinary osmolality and increased urine flow so that urinary Na(+) excretion increased with no effect on urinary Na(+) concentration. This decrease in urinary concentration further increased plasma Na(+) concentration, osmolality, and AVP concentration in these already hypernatremic mice. Benzamil similarly compromised urinary concentration in water-deprived mice and in mice treated with desmopressin. These results demonstrate that stimulation of ENaC by AVP plays a critical role in water homeostasis by facilitating urinary concentration, which can compensate for hypernatremia or exacerbate hyponatremia. The present findings are consistent with ENaC in addition to serving as a final effector of the renin-angiotensin-aldosterone system and blood pressure homeostasis, also playing a key role in water homeostasis by regulating urine concentration and dilution of plasma.

Additive effects of Capsaicin Oleoresin, Irbesartan and Amlodipine Besylate on the blood pressure of spontaneously hypertensive rats

“…Reduction in aldosterone catabolism results in volume retention, leading to an increase in SBP. A similar pattern is also seen with AVP urine out, thus confirming volume retention as a likely inducer of hypertension in SHR (Mironova, et al, 2015). Collectively, the observations are consistent with studies showing that the activation of adrenal afferent nerves in vivo attenuated aldosterone steroidogenesis, and that high levels of ACTH prevented this phenomenon (Ulrich-Lai et al, 2001).…”

Vasopressin regulation of sodium transport in the distal nephron and collecting duct

“…Although benzamil increased urinary sodium excretion, plasma sodium concentrations were increased. Benzamil treatment of water-deprived mice and dDAVP-treated mice also resulted in reduced urinary concentration (178), demonstrating that stimulation of ENaC by AVP plays an important role in water homeostasis. Similarly to the mechanisms described for NCC (see above), stimulation of ENaC is predicted to decrease the tonicity of the tubular fluid and (marginally) increase the tonicity in the surrounding interstitium.…”

“…In contrast, CD-specific ␣-ENaC knockout does not have impaired sodium reabsorption or differences in urine osmolality (240), arguing that ␣-ENaC function in the CNT is essential for full urine concentrating ability (47). In mice on a high-sodium diet treated with the ENaC blocker benzamil, urine osmolality was decreased alongside increased urine flow (178). Although benzamil increased urinary sodium excretion, plasma sodium concentrations were increased.…”

Coordinated Regulation of Vasopressin Inactivation and Glucose Uptake by Action of TUG Protein in Muscle

“…Therefore, increased copeptin concentrations in insulinresistant individuals may reflect, at least in part, accelerated inactivation of vasopressin, together with a compensatory increase in vasopressin secretion. Whether this may contribute to hypertension in the setting of insulin resistance is not known, and is worthy of further study (35,47,48).…”