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(Hypertension. 1995;25:1238-1244.)
© 1995 American Heart Association, Inc.

Articles

Association Between the Natriuretic Action of Angiotensin-(1-7) and Selective Stimulation of Renal Prostaglandin I₂ Release

Sean D. Hilchey; Caroline P. Bell-Quilley

From the Department of Pharmacology, New York Medical College, Valhalla.

Correspondence to Caroline P. Bell-Quilley, PhD, Safety Pharmacology, SmithKline Beecham Pharmaceuticals, 709 Swedeland Rd, PO Box 1539, King of Prussia, PA 19406-0939.

Abstract We previously reported that angiotensin-(1-7) [Ang-(1-7)], a heptapeptide derived from the metabolism of either Ang I or Ang II, was biologically active in the rat isolated kidney, producing a marked diuresis and natriuresis that could be dissociated from the modest increase in glomerular filtration rate. The natriuretic response was accompanied by an increase in sodium concentration and concomitant decrease in urinary potassium concentration. Ang-(1-7) has also been shown to stimulate arachidonic acid release from isolated proximal tubules and elicit prostaglandin release from a number of tissues. Therefore, in the present study we tested the hypothesis that prostaglandins participate in the renal actions of Ang-(1-7). Rat isolated kidneys were perfused at 37°C with gassed (95% O₂/5% CO₂) Krebs-Henseleit buffer containing oncotic agents and amino acids for six 10-minute clearance periods 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 absence of 10 µmol/L indomethacin. Prostaglandin E₂ (PGE₂) and PGI₂ released into ureteral and venous effluents were measured by enzyme-linked immunoassay. During Ang-(1-7) infusion there was a selective increase in 6-keto-PGF₁, an index of PGI₂, appearing in both urine and perfusate; PGE₂ levels were unchanged. Inhibition of stimulated 6-keto-PGF₁ release with indomethacin halved the fourfold increase in urine flow and sevenfold increase in sodium excretion rate without altering the increase in urinary sodium concentration produced by Ang-(1-7). In contrast, the increased potassium excretion rate 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 PGI₂ versus PGE₂ 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 concentration. It is possible that these observations have relevance to the link between prostaglandins and converting enzyme inhibitors in view of earlier reports that these antihypertensive agents substantially increase Ang-(1-7).

Key Words: angiotensins • natriuresis • indomethacin • prostaglandins • immunoenzyme techniques • kidney • rats

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