Comparative Effect of PGE ₂ and PGI ₂ on Renal Function

Abstract

Rapid degradation of prostacyclin (PGI2) inherent to its molecular structure has long been a major limitation in assessing the natriuretic effect of this prostaglandin. The recent availability of the stable PGI2 analogue iloprost now allows for a comparative study with prostaglandin E2 (PGE2). In the present study conducted in six anesthetized dogs, the intrarenal effects of two consecutive doses (1 and 4 ng x kg(-1) x min(-1)) of PGE2 on renal blood flow, glomerular filtration rate, and urinary sodium excretion were compared with the effects of two identical doses of iloprost. The selected doses of PGE2 were those producing a maximal natriuretic and vasodilator response without affecting mean arterial pressure. A washout period was allowed between administration of PGE2 and iloprost. PGE2 infusion significantly increased fractional sodium excretion from 0.69+/-0.1 to 2.79+/-1.1% and 4.27+/-1.2%% (P<.05), respectively. These changes in fractional sodium excretion induced by PGE2 were associated with significant increases in renal blood flow from 151.1+/-62 to 185+/-64.3 and 185.6+/-64.3 mL/min (P<.05), respectively; however, no significant alterations were seen in glomerular filtration rate, from 29.5+/-9.4 to 35.2+/-12.2 and 32.7+/-7.8 mL/min (NS), and mean arterial pressure, from 117.6+/-26 to 113.9+/-24.1 and 112.3+/-24.1 mm Hg (NS) during control and PGE2 infusion. At identical doses, sequential infusion of PGI2 had no effect on renal blood floww and glomerular filtration rate, producing natriuresis only at the highest dose, a fractional sodium excretion from 0.69+/-0.1 to 0.8+/-0.28 mm Hg (NS) and 1.05+/-0.34% (P<.05), respectively. In conclusion, the present study confirms that PGE2 exerts a natriuretic effect during increases in renal blood flow. In contrast, PGI2 had no hemodynamic effect, and the natriuresis was markedly blunted.

Effect of a Prostacyclin Analogue, Iloprost, on Urinary Aquaporin-2 Excretion in Humans

“…The finding does, however, support the hypothesis that iloprost has a natriuretic effect, thus explaining the increase in urinary output reported by other authors [20]. Moreover, we found in our experimental model that iloprost increased the urinary flow rate, as also observed by Ylitalo et al [21], and this increase should be considered secondary to the direct action of iloprost.…”

Prostaglandin E 2 Mediates Connecting Tubule Glomerular Feedback

“…Here, we found that CTGF is mediated by PGE 2 . Our data is consistent with previous reports that PGE 2 influences renal vascular resistance, causing an increase in renal vascular cAMP levels and inducing relaxation of preglomerular vessels 24,25 , while PGI 2 was a less likely candidate to mediate CTGF because it is less potent as a renal vasodilator 13,26 . Furthermore, our finding that CTGF prostanoids are derived from the CNT rather than the Af-Art endothelium (see below), supports the hypothesis that PGE 2 is the mediator of CTGF, since PCR studies have shown that connecting tubules express mPGES, the enzyme that synthesizes PGE 2 , while PGI 2 synthase is not expressed in the nephron 27 .…”

Novel role of AQP-1 in NO-dependent vasorelaxation

“…This would result in enhanced NO concentrations, which in turn would increase diffusion, thus enhancing the effects of NO in vascular smooth muscle cells. Third, other modulators of vascular tone, such as prostaglandins (5,11,21,63), carbon monoxide (CO) (8,29,67,68), cytochrome P-450 epoxygenase products (15,27,66), and endothelium-dependent hyperpolarizing factor (48,64), could be upregulated in the knockouts, mitigating the reduced vasodilator effect of NO in the vasculature. Finally, other aquaporins may compensate for the lack of AQP-1 within the vasculature.…”