Permissive Action of Glucocorticoid Substitution Therapy on the Effects of Atrial Natriuretic Peptide (hANP) in Patients with Adrenocortical Insufficiency

Abstract

To study the potential impact of glucocorticoids on the effects of human atrial natriuretic peptide (hANP) in man, the diuretic and natriuretic response to intravenous bolus doses of hANP (50 and 100 micrograms) was studied in seven male patients with deficient endogenous glucocorticoid synthesis, both during withdrawal of glucocorticoid therapy and during subsequent substitution with dexamethasone. Plasma concentrations of ACTH, though markedly suppressed by dexamethasone as compared to the unsubstituted state were not influenced by exogenous hANP either during deprival or substitution of glucocorticoids. Basal plasma concentrations of hANP were 10.3 +/- 8.4 pmol/l and 19.3 +/- 11.1 pmol/l during glucocorticoid withdrawal and following substitution with dexamethasone, respectively. When substituted with glucocorticoids, patients responded to hANP (100 micrograms) with an increase (p less than 0.025) in diuresis and sodium excretion, whereas no changes in diuresis and sodium excretion were seen following intravenous hANP during glucocorticoid withdrawal. These results suggest that glucocorticoids may have a permissive effect on hANP-mediated natriuresis and diuresis.

Potent diuretic effects of prednisone in heart failure patients with refractory diuretic resistance

“…It has been reported that glucocorticoids can regulate the synthesis and release of ANP (5), upregulate ANP receptors on vascular endothelial cells (6) and potentiate the response of cyclic GMP to ANP (9). A human study indicated that glucocorticoids may have a permissive effect on human ANP-mediated natriuresis and diuresis (10). An observational study designed to detect the relationship between ANP and Cushing's syndrome also revealed that ANP levels in patients with Cushing's syndrome were three times higher than in the normal population, which is in accordance with our postulation above (11).…”

Glucocorticoids Improve Renal Responsiveness to Atrial Natriuretic Peptide by Up-Regulating Natriuretic Peptide Receptor-A Expression in the Renal Inner Medullary Collecting Duct in Decompensated Heart Failure

“…Our findings were also supported by data from humans. Damjancic and Vierhapper (1990) reported glucocorticoids could potentiate renal responsiveness to ANP in humans with adrenocortical insufficiency, therefore leading to a dramatic increase in natriuresis and diuresis. Massari et al (2011) reported that methylprednisolone induced potent diuretic effect in a patient with severe heart failure but lowered natriuretic peptide levels in the circulation at the same time, suggesting glucocorticoid might have a role in natriuretic peptide system.…”

Association between glucocorticoid use and all-cause mortality in critically ill patients with heart failure: A cohort study based on the MIMIC-III database

“…Glucocorticoids can also protect kidney function. Previous studies have found that glucocorticoids dilate renal blood vessels, enhance the sensitivity of nephrons to diuretics, and increase the GFR ( Liu et al, 2007 ; Smets et al, 2012 ; Liu et al, 2016 ), via the following mechanisms: First, glucocorticoids upregulate natriuretic peptide receptor A expression in the inner medullary collecting duct cells to enhance the sensitivity of the kidneys to natriuretic peptides and promote the diuretic effect in patients with HF ( Gardner et al, 1986 ; Damjancic and Vierhapper, 1990a ; Liu et al, 2010 ; Liu et al, 2011 ). Second, glucocorticoids reduce the production and secretion of vasopressin, and downregulate arginine vasopressin receptor expression ( Erkut et al, 1998 ; Liu et al, 2006b ; Greenwood et al, 2015 ; Zhu et al, 2020 ); the production of prostaglandins, nitric oxide, and dopamine is also increased, resulting in improved renal blood flow and GFR ( Gong et al, 2008 ; Tokudome et al, 2009 ; Butts and Phillips, 2013 ; Liu et al, 2019b ).…”