In heart failure, phosphodiesterase V (PDEV) was elevated, resulting in increased cGMP degradation and impaired natriuresis. In animal research, PDEV inhibition increased the renal response to B-type natriuretic peptides. In patients with pre–heart failure, researchers evaluated the hypothesis that long–term PDEV inhibition would have improved renal function and cardiorenal responsiveness following a short–term volume load. A total of 20 people with pre–heart failure (defined as an ejection fraction of less than or equal to 45% without a previous diagnosis of heart failure) and renal impairment were randomly assigned to either tadalafil or placebo in a 2:1 ratio. A baseline echocardiogram and renal clearance research were done, followed by a brief saline load and additional echocardiography and renal clearance testing. After 12 weeks, the subjects were given either tadalafil at a goal dose of 20 mg daily or a placebo, and the research day was repeated. The glomerular filtration rate was not improved by long-term tadalafil (median increase of 2.0 mL/min in the tadalafil group against 13.5 mL/min in the placebo group; P=0.54). There was no difference in urine sodium or cGMP excretion following short-term saline loading when PDEV inhibition was used. After 12 weeks of tadalafil, glomerular filtration rate and urine sodium/cGMP excretion were not substantially different from placebo. The outcomes did not support the use of PDEV inhibition to improve renal responsiveness in individuals with pre–heart failure.