Activating soluble guanylyl cyclase attenuates ischemic kidney damage.

Can direct activation of soluble guanylyl cyclase (sGC) provide kidney-protection? To answer this, we tested the kidney-protective effects of a sGC activator, which functions independent of nitric oxide and with oxidized sGC, in an acute kidney injury (AKI) model with transition to chronic kidney disease (CKD). We hypothesize this treatment would provide protection of kidney microvasculature, kidney blood flow, fibrosis, inflammation, and kidney damage. Assessment took place on days three, seven, 14 (acute phase) and 84 (late phase) after unilateral ischemia reperfusion injury (IRI) in rats.

Piezo1 Mediates Vasodilation Induced by Acute Hyperglycemia in Mouse Renal Arteries and Microvessels.

Background: Acute hyperglycemia is a risk factor for developing acute kidney injury and poor renal outcome in critically ill patients, whereby the role of renal vasculature remains unclear. We hypothesize that hyperglycemia-associated hyperosmolarity facilitates vasodilation through Piezo1-mediated eNOS (endothelial NO synthase) activation.

Methods: Vasoreactivity was analyzed using wire myography in isolated mouse mesenteric arteries and renal interlobar, and using microvascular perfusion in renal afferent arterioles and efferent arterioles, and vasa recta.

Nitric Oxide Signalling in Descending Vasa Recta after Hypoxia/Re-Oxygenation.

Reduced renal medullary oxygen supply is a key factor in the pathogenesis of acute kidney injury (AKI). As the medulla exclusively receives blood through descending vasa recta (DVR), dilating these microvessels after AKI may help in renoprotection by restoring renal medullary blood flow. We stimulated the NO-sGC-cGMP signalling pathway in DVR at three different levels before and after hypoxia/re-oxygenation (H/R).

Age Impairs Soluble Guanylyl Cyclase Function in Mouse Mesenteric Arteries.

Endothelial dysfunction (ED) comes with age, even without overt vessel damage such as that which occurs in atherosclerosis and diabetic vasculopathy. We hypothesized that aging would affect the downstream signalling of the endothelial nitric oxide (NO) system in the vascular smooth muscle (VSM). With this in mind, resistance mesenteric arteries were isolated from 13-week (juvenile) and 40-week-old (aged) mice and tested under isometric conditions using wire myography.

Protective Effect of Tempol on Acute Kidney Injury Through PI3K/Akt/Nrf2 Signaling Pathway.

Background/aims: Tempol is a protective antioxidant against ischemic injury in many animal models. The molecular mechanisms are not well understood. Nuclear factor erythroid 2-related factor (Nrf2) is a master transcription factor during oxidative stress, which is enhanced by activation of protein kinase C (PKC) pathway.