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- Title
Opposite renal effects of a PGE<sub>1</sub> analog and prostacyclin in humans.
- Authors
Natov, Svetlozar; Schmitt, François; Ikeni, Achour; Lacour, Bernard; Hannedouche, Thierry P.
- Abstract
Renal effects of prostaglandins have been widely investigated in anesthetized animals, but in contrast only few studies have been devoted to healthy and diseased humans. Recently, both prostacyclin and a stable analog of PGE1, misoprostol, have been available for therapeutic purposes in clinical conditions associated with peripheral or renal vasoconstriction: however, the renal effects have not been defined. We have therefore studied the acute renal effects of PGI2 5 ng · kg/min intravenously and of misoprostol, a stable PGE, analogue, 400 #x03BC;orally in two groups of respectively 8 and 12 healthy supine subjects on normal sodium diet using sodium, lithium, inulin, PAH and neutral dextran clearances. PGI2 induced a slight natriuretic effect, a systemic and renal vasodilation with a decrease in mean arterial pressure from 85.3 ± 1.1 to 80.2 ± 1.6 mm Hg (P < 0.01) and in renal vascular resistance from 94 ± 6 to 75 ± 5 mm Hg · min/ml (P < 0.001). GFR did not change whereas fractional clearance of dextran decreased over the 34 to 48 A radius range. Applying these changes on a hydrodynamic model of filtration of macromolecules through water-filled pores, we calculated that PGI2 decreased the glomerular transcapillary pressure gradient from 35 ± 1 to 32 ± 1 mm Hg (P < 0.001), decreased nonsignificantly the ultrafiltration coefficient Kf and did not affect the membrane parameters r0 and ω0. Misoprostol had no natriuretic effect, induced slight renal vasoconstriction and moderate decrease in GFR from 124 ± 9 to 114 ± 10 ml/min · 1.73 m² (P #x003C; 0.001). Fractional dextran clearances were depressed over the 36 to 42 A radius range corresponding to a rise in AP from 34 ± 1 to 39 ± 2 mm Hg (P < 0.01), a decrease in Kf and no change in r0 and ω0. Most of these changes are likely related to a stimulatory effect of angiotensin II production since plasma renin activity increased consistently after administration of misoprostol. Thus, prostacyclin and misoprostol exerted contrasting effects on renal function in healthy humans; these effects are likely related to depressed baseline renal vascular tone, and to the ability or not to stimulate renin release in this condition.
- Subjects
PROSTAGLANDINS; KIDNEY diseases; DEXTRAN; NATRIURESIS; VASODILATION; ARTERIES
- Publication
Kidney International, 1994, Vol 45, Issue 5, p1457
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1038/ki.1994.190