Association between the natriuretic action of angiotensin-(1-7) and selective stimulation of renal prostaglandin I2 release.
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 degrees 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 mumol/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 alpha, an index of PGI2, appearing in both urine and perfusate; PGE2 levels were unchanged. Inhibition of stimulated 6-keto-PGF1 alpha 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).(ABSTRACT TRUNCATED AT 250 WORDS)
Hilchey
S D
SD
Department of Pharmacology, New York Medical College, Valhalla, USA.
Bell-Quilley
C P
CP
D015121:6-Ketoprostaglandin F1 alpha / Q000494:pharmacology; D000803:Angiotensin I; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001834:Body Water / Q000378:metabolism; D004573:Electrolytes / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D004573:Electrolytes; D010446:Peptide Fragments; D000804:Angiotensin II; D015121:6-Ketoprostaglandin F1 alpha; D000803:Angiotensin I; D011464:Epoprostenol; C118790:angiotensin I (1-7); D007213:Indomethacin