Effects of microsomal prostaglandin E synthase‐1 inhibition on resistance artery tone in patients with end stage kidney disease

Abstract

Background: The microvasculature is a target organ for the early manifestations of cardiovascular disease. Therefore, a better understanding of the prostaglandin system and characterising the effects of mPGES-1 inhibition and concomitant reduction of PGE 2 in vascular beds are of interest.Experimental Approach: The effects of mPGES-1 inhibition on constriction and relaxation of resistance arteries (diameter: 100-400 μm) from patients with end stage kidney disease (ESKD) and controls (Non-ESKD) were studied using wire-myography in combination with immunological and mass-spectrometry based analyses.

Uso de ibuprofeno en el tratamiento de pacientes pediátricos con poliuria y disnatremia. Reporte de una serie de casos

“…Ambas enzimas estimulan la síntesis de PGI2; PGE2, causan vasodilatación y mejoría de la oxigenación en la médula renal. 5,14 Además, la PGE2 aumenta la diuresis y la excreción de sodio activando los receptores tubulares, bloqueando el transporte de sodio y cloro en el asa ascendente de Henle y en los conductos colectores, donde también antagoniza los efectos sobre el tráfico de AQP2 a través del receptor EP3. 15 Frente a la coexistencia de DIC y SPS, nosotros implementamos un tratamiento secuencial sintomático destinado a restaurar el equilibrio hidroelectrolítico, considerando que la poliuria prolongada, en la DIC y en el SPS, puede "lavar" el gradiente túbulo intersticial medular 16,17 y promover incluso la aparición de un tipo de diabetes insípida nefrogénica secundaria y no asociada a la producción y/o la expresión de la acuaporina.…”

Microsomal prostaglandin E synthase‐1 inhibition prevents adverse cardiac remodelling after myocardial infarction in mice

“…Nevertheless, in vivo studies of cardiovascular diseases investigating the effects of pharmacological inhibition of mPGES‐1 are lacking. We and others have recently shown in ex vivo experiments assessing the vascular tone that treatment with mPGES‐1 inhibitors resulted in reduced vasoconstriction in larger human vessels (saphenous vein and internal mammary artery), associated with shunting to PGI 2 (Ozen et al, 2017), as well as in human resistance arteries (Larsson et al, 2019; Steinmetz‐Späh et al, 2021). In comparison, inhibition of COX‐2 has been shown to enhance vascular tone in larger human blood vessels and intrarenal arcuate arteries from mice (Kirkby et al, 2018; Ozen et al, 2017).…”

Biosynthesis of prostaglandin 15dPGJ2 -glutathione and 15dPGJ2-cysteine conjugates in macrophages and mast cells via MGST3

“…Unlike nonsteroidal anti-inflammatory drugs, which target cyclooxygenases (COX) and suppress all downstream prostaglandins, selective mPGES-1 inhibition prevents the formation of induced PGE 2 biosynthesis but spares other prostaglandins and may also lead to increased biosynthesis of anti-inflammatory arachidonic acid metabolites. The resulting changes in prostaglandin profiles observed in various cell types including cancer cells, fibroblasts, macrophages, and vessels raise the possibility of cardiovascular protection and enhanced anti-inflammatory effects following mPGES-1 inhibition ( 1 , 2 , 3 , 4 , 5 , 6 , 7 ). Previously, we showed that the eicosanoid profile is altered in lipopolysaccharides (LPS)-treated peritoneal macrophages from mPGES-1 KO mice compared with cells from WT mice.…”