Induction Of Renal Tumor Necrosis Factor-A And Other Autacoids And The Beneficial Effects Of Hypertonic Saline In Acute Decompensated Heart Failure

Although administration of hypertonic saline (HSS) in combination with diuretics has yielded improved weight loss, preservation of renal function, and reduction in hospitalization time in the clinical setting of patients with acute decompensated heart failure (ADHF), the mechanisms that underlie these beneficial effects remain unclear and additional studies are needed before this approach can be adopted on a more consistent basis. As high salt conditions stimulate the production of several renal autacoids that exhibit natriuretic effects, renal physiologists can contribute to the understanding of mechanisms by which HSS leads to increased diuresis both as an individual therapy as well as in combination with loop diuretics. For instance, since HSS increases TNF-alpha production by proximal tubule and thick ascending limb of Henle's loop epithelial cells, this article is aimed at highlighting how the effects of TNF-alpha produced by these cell types may contribute to the beneficial effects of HSS in patients with ADHF. Although TNF-alpha produced by infiltrating macrophages and T cells exacerbates and attenuates renal damage, respectively, production of this cytokine within the tubular compartment of the kidney functions as an intrinsic regulator of blood pressure and Na+ homeostasis via mechanisms along the nephron related to inhibition of Na+-K+-2Cl(-) cotransporter isoform 2 activity and angiotensinogen expression. Thus, in the clinical setting of ADHF and hyponatremia, induction of TNF-alpha production along the nephron by administration of HSS may attenuate Na+-K+-2Cl(-) cotransporter isoform 2 activity and angiotensinogen expression as part of a mechanism that prevents excessive Na thorn reabsorption in the thick ascending limb of Henle's loop, thereby mitigating volume overload.