The renal vasodilatory effect of prostaglandins is ameliorated in isolated-perfused kidneys of endotoxemic mice

Abstract

Endotoxemia-related acute kidney injury (AKI) is associated with increased formation of prostaglandins, which may serve as a compensatory mechanism to maintain renal function. We hypothesized that an increase of renal EP or EP receptors and/or a downregulation of renal EP and EP receptors enhances PGE-induced renal vasodilatation. Injection of lipopolysaccharide (LPS; 3 mg/kg i.p.) increased microsomal prostaglandin E synthase (mPGES)-1 and prostacyclin synthase expression, whereas mPGES-2 expression was unaltered. Further, LPS increased the mRNA abundance for the prostaglandin EP receptor, whereas the expressions of the EP and EP receptors were decreased. In isolated-perfused kidneys from control mice, PGE exerted a dual effect on renal vascular tone, inducing vasodilatation at lower concentrations and vasoconstriction at higher concentrations. In kidneys from endotoxemic mice, the vasodilatory component was more pronounced, whereas the vasoconstriction at higher PGE concentrations was absent. Similarly, prostacyclin (PGI)-induced vasodilatation was more pronounced in endotoxemic kidneys. The enhanced vasodilatory effect was paralleled by an increase in renal vascular EP and prostacyclin IP receptor mRNA expression. Further, stimulation of renin secretion rate by PGE and PGI was enhanced in endotoxemic kidneys. Pretreatment with the cyclooxygenase (COX)-2 inhibitor SC-236 (10 mg/kg) did not alter the basal GFR, but augmented the LPS-induced decline in GFR, and attenuated the LPS-induced increase in plasma renin concentration in vivo. Our data suggest that an activation of the COX-2/mPGES-1 synthetic pathway is responsible for the increased renal formation of PGE in response to LPS and that the vasodilatory effect of PGE and PGI is enhanced during endotoxemia.

Differential properties of E prostanoid receptor‐3 and thromboxane prostanoid receptor in activation by prostacyclin to evoke vasoconstrictor response in the mouse renal vasculature

“…In contrast to findings of the present study, one prior report showed that iloprost increases the basal flow (obtained under un‐precontracted conditions) in perfused kidneys, especially those of mice with endotoxemia 49 . Another study also revealed that bolus injection of PGI 2 causes contractile activity, which is, however, followed by a relaxation under perfusion with another vasoconstrictor methoxamine 50 .…”

PGE2 pathway mediates oxidative stress‐induced ferroptosis in renal tubular epithelial cells

“…The prostaglandins, once formed, are released quickly out of cells, and are assumed to work in the vicinity of their sites of production as a result of their chemical and metabolic instability. Several studies have confirmed that PGE2 plays an important role in the occurrence and development of AKI [36,41,42]. Consistent with previous studies, our results showed that, during H 2 O 2 -induced ferroptosis in HK-2 cells, PGE2 content in supernatant increases, and PGE2 pathway changes were detected during ferroptosis in HK-2 cells.…”

“…Studies have reported an association between AKI and the rise of prostaglandins. PGE2 pathway can regulate the therapeutic effect of AKI induced by IRI in mice [36,37]. However, it is not clear whether the PGE2 pathway is associated with ferroptosis in AKI.…”

Indoleamine-2,3-Dioxygenase Activates Wnt/β-Catenin Inducing Kidney Fibrosis after Acute Kidney Injury

“…Coincidentally, LPS-induced kidney injury model revealed increased PGE2 level indicating PGE2 may be a risk factor for kidney injury [41]. However, Meurer et al [42] indicated that PGE2 could maintain GFR and renal perfusion by dilating the renal afferent arteriole. In addition, their study indicated elevated expressions of PGE2 and vasodilatation in endotoxemia-related acute kidney injury by injecting LPS in mice.…”