Conditions like heart failure that augment the activity of neurohumoral mechanisms i.e. the renin-angiotensin systems, sympathetic nerve activity and vasopressin secretion are commonly associated with a decreased effective blood volume and a reduced renal perfusion. This leads to an increased dependence of renal hemodynamics on endogenous renal prostaglandin synthesis as a vasodilator and natriuretic counter-regulating system. We investigated the role of prostaglandins in renal functional control in an experimental setting of congestive heart failure by chronic inhibition of cyclooxygenase by indomethacin. In chronic moderate heart failure plasma levels of prostaglandin E2 and prostacyclin were unchanged whereas the urinary excretion of prostaglandin E2 was significantly increased, indicating an augmented synthesis within the kidney (Figures 1 to 3). After inhibition of prostaglandin synthesis we observed a profound increase of renal vascular resistance associated with a reduction of effective renal plasma flow and renal blood flow. This was mainly due to a constriction of the vas afferens of the glomerulum. This led to an impairment of renal function indicated by an increase of serum creatinine and blood urea nitrogen associated with a reduction of urinary flow and fluid retention (Figures 4 and 5). We also studied in a randomized, double-blind, placebo-controlled, parallel-group trial in 40 patients with congestive heart failure effects of acetylsalicylic acid (500 mg t.i.d.) on renal functional parameters. In patients with normal sodium intake acetylsalicylic acid reduced urinary prostaglandin E2 concentration by 37% which led to a reduction of daily urinary sodium excretion by 29% in comparison to placebo (Figure 6). These results clearly show the importance of vasodilator prostaglandins in the regulation of kidney function in heart failure where inhibition of cyclooxygenase results in profound deterioration of renal perfusion and kidney function and retention of fluid and sodium.