ASSOCIATION BETWEEN THE NATRIURETIC ACTION OF ANGIOTENSIN-(1-7) AND SELECTIVE STIMULATION OF RENAL PROSTAGLANDIN I-2 RELEASE

We previously reported that angiotensin-(1-7) [Ang-(1-7)], a heptapept ide derived from the metabolism of either Ang I or Ang II, was biologi cally active in the rat isolated kidney, producing a marked diuresis a nd natriuresis that could be dissociated from the modest increase in g lomerular filtration rate. The natriuretic response was accompanied by an increase in sodium concentration and concomitant decrease in urina ry potassium concentration. Ang-(1-7) has also been shown to stimulate arachidonic acid release from isolated proximal tubules and elicit pr ostaglandin release from a number of tissues. Therefore, in the presen t study we tested the hypothesis that prostaglandins participate in th e renal actions of Ang-(1-7). Rat isolated kidneys were perfused at 37 degrees C with gassed (95% 0(2)/5% CO2) Krebs-Henseleit buffer contai ning oncotic agents and amino acids for six 10-minute clearance period s at a constant pressure of 90 mm Hg. Ang-(1-7) was infused at a rate that achieved a final concentration of 3 pmol/mL in the presence and a bsence of 10 mu mol/L indomethacin. Prostaglandin E(2) (PGE(2)) and PG I(2) released into ureteral and venous effluents were measured by enzy me-linked immunoassay. During Ang-(1-7) infusion there was a selective increase in 6-keto-PGF(1 alpha), an index of PGI(2), appearing in bot h urine and perfusate; PGE(2) levels were unchanged. Inhibition of sti mulated 6-keto-PGF(1 alpha) release with indomethacin halved the fourf old increase in urine flow and sevenfold increase in sodium excretion rate without altering the increase in urinary sodium concentration pro duced by Ang-(1-7). In contrast, the increased potassium excretion rat e was unchanged, despite the reduction in urine flow, as indomethacin abolished the fall in urinary potassium concentration caused by Ang-(1 -7) infusion alone. Thus, Ang-(1-7) is a specific stimulus for renal P GI(2) versus PGE(2) release. This effect may mediate Ang-(1-7)-induced natriuresis and diuresis and fall in urinary potassium concentration but does not appear to be involved in the doubling of urinary sodium c oncentration. It is possible that these observations have relevance to the link between prostaglandins and converting enzyme inhibitors in v iew of earlier reports that these antihypertensive agents substantiall y increase Ang-(1-7).