Renal prostaglandin synthesis in the Goldblatt hypertensive rat.
The role of prostaglandins in blood pressure regulation was studied in normal rats and in animals with renal artery constriction. The effects of chronic inhibition of prostaglandin (PG) synthesis on arterial pressure were observed, and renal medullary PG synthesis was measured in vitro. The prostaglandin synthetase inhibitor indomethacin was given in a dose of 2 mg/kg/day by mouth to one of two groups of male Wistar rats with a unilateral renal artery constriction and the other kidney untouched, and to one of two sham-clipped groups. Systolic blood pressures were higher in indomethacin-treated clipped rats than in non-indomethacin-treated clipped animals, and at 18 days averaged 188 mm Hg (plus or minus SEM 5.9, n = 36) and 162 mm Hg (plus or minus SEM 7.6, n = 34), respectively (P less than 0.005 for data pooled from two experiments). Indomethacin did not affect pressures of sham-clipped animals treated for 40 days. Analysis of PG synthesis by gas-liquid chromatography in renal medullary slices incubated for 30 minutes in Krebs-Henseleit buffer showed: (1) 40% suppression of PGE synthesis in hypertensive animals (P less than 0.001): (2) no differences between clipped and untouched kidneys; (3) chronic indomethacin treatment did not affect PGE synthesis in the in vitro buffer system; and (4) no PGA synthesis was detected. In a further experiment in which medullary slices were incubated in plasma of rats treated with equivalent doses of indomethacin, PGE synthesis was suppressed by 35%. The experiments support the concept that prostaglandins modulate pressor mechanisms which come into play when renal blood flow is drastically reduced. The effects could be mediated by PG synthesis in the kidney and/or in other systemic vascular beds.
D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D002849:Chromatography, Gas; D004326:Drinking; D006977:Hypertension, Renal / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis; D051381:Rats; D012078:Renal Artery Obstruction / Q000378:metabolism; D012964:Sodium / Q000097:blood; D014508:Urea / Q000097:blood
D011453:Prostaglandins; D011458:Prostaglandins E; D014508:Urea; D012964:Sodium; D007213:Indomethacin