Cardiac Versus Renal Response to Volume Expansion in Preclinical Systolic Dysfunction With PDEV Inhibition and BNP

Abstract

Visual Abstract

Paradoxical Cardiorenal Responses Following Acute Vasodilator/Natriuretic Treatment in Presystolic Heart Failure

“…The divergent responses between the heart and the kidney in the study by Wan et al. (2) may also relate to acute hemodynamic accommodation to changes in blood pressure. Specifically, there was a large drop in systolic blood pressure within the normal range from 125 to 112 mm Hg that was not seen in the placebo group.…”

“…Given the data from the current study (2), potential mechanisms for impaired renal response to acute volume expansion in patients with PSD include decreased plasma atrial natriuretic peptide levels, up-regulation of PDE5 leading to greater degradation of cGMP, down-regulation of natriuretic peptides in the kidney, and up-regulation of neutral endopeptidases leading to disruption of the homeostasis of natriuretic peptides with downstream effects within the nephron. This latter hypothesis seems most plausible based on data regarding cGMP levels in the combination group.…”

“…As the authors speculate (2), PDE5 metabolizes cGMP, a second messenger that leads to vascular smooth muscle relaxation and subsequent vasodilation. Renal cGMP plays an important role in modulating glomerular filtration rate (GFR) and natriuresis.…”

“…The current study by Wan et al. (2) in this issue of JACC: Basic to Translational Science describes the acute cardiorenal effects of combining tadalafil, a phosphodiesterase-5 inhibitor (PDE5i), with nesiritide, a recombinant human B-type natriuretic peptide (BNP), in response to acute saline volume expansion in participants with preclinical systolic dysfunction (PSD) and stages 2 and 3A chronic kidney disease (CKD). The authors hypothesized that this combination would enhance the cardiorenal response to volume expansion in PSD compared with a PDE5i alone.…”

“…First, we need to understand the neurohormonal changes that affect the heart and the kidney at this stage of heart failure in the presence of CKD. As the authors note (2), the neurohumoral profile of their cohort is reminiscent of those in the SOLVD (Studies of Left Ventricular Dysfunction) Prevention cohort; that is, mild activation of the natriuretic peptide system and no activation of the renin-angiotensin-aldosterone system. An impaired renal response to acute volume expansion in the patients with PSD compared with normal subjects is known.…”