Opposite renal effects of a PGE1 analog and prostacyclin in humans

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 PGE1 analogue, 400 micrograms 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 omega 0. 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 < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of the prostacyclin analogue iloprost on cyclosporin-induced renal hypoperfusion in stable renal transplant recipients

“…To our knowledge, the impact of infusion of a PGI 2 analogue has not previous been investigated in CsA-treated subjects, but studies in patients with essential hypertension and thrombangiitis obliterans have likewise demonstrated systemic [12,13] and renal vasodilatation [13] by infusion of iloprost in the same dose as the present study, but have contrary to our findings also demonstrated a large increase in GFR [12,13], and a significant increase in the filtration fraction [13]. More comparable with the present results is the study of Natov et al, who investigated the effect of PGI 2infusion in normal volunteers, and demonstrated a decrease in arterial blood pressure, an increase in renal plasma flow, with no change in GFR, and a decrease in filtration fraction [15]. It seems paradoxical that iloprost should abolish CsA-induced vasoconstriction without any impact on the decline in GFR.…”

Exacerbation of Celecoxib-Induced Renal Injury by Concomitant Administration of Misoprostol in Rats

“…Interestingly, when rat blood pressure was measured on day 9, there was a significant rise in diastolic, systolic, and mean pressure in the misoprostol+misoprostol group when compared to vehicle+vehicle group (Table 3). The influence of misoprostol on blood pressure can be explained by the renal vasoconstriction effect of misoprostol [58]. Furthermore, when misoprostol was co-administered with celecoxib, these blood pressure parameters were further elevated.…”

Eicosanoid regulation of the renal vasculature

“…This possibility has been suggested by studies in EP 3 gene-disrupted mice that show a prolonged systemic vasodepressor response to PGE 2 administration that is more pronounced in male mice (10). EP 3 receptor activation may also have renal hemodynamic actions because misoprostol, an EP 2 -, EP 3 -, and EP 4receptor agonist, causes a slight vasoconstriction and decreased glomerular filtration rate in humans (109). Additionally, mice that lack the EP 3 receptor have elevated renal blood flows compared with wild-type mice (9).…”