Search

Acute kidney injury (AKI) and chronic kidney disease (CKD) are increasingly recognized as interconnected conditions with overlapping pathophysiological mechanisms. This review examines the transition from AKI to CKD, focusing on the molecular mechanisms, animal models, and biomarkers essential for understanding and managing this progression. AKI often progresses to CKD due to maladaptive repair processes, persistent inflammation, and fibrosis, with both conditions sharing common pathways involving cell death, inflammation, and extracellular matrix (ECM) deposition. Current animal models, including ischemia-reperfusion injury (IRI) and nephrotoxic damage, help elucidate these mechanisms but have limitations in replicating the complexity of human disease. Emerging biomarkers such as kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and soluble tumor necrosis factor receptors (TNFRs) show promise in early detection and monitoring of disease progression. This review highlights the need for improved animal models and biomarker validation to better mimic human disease and enhance clinical translation. Advancing our understanding of the AKI-to-CKD transition through targeted therapies and refined research approaches holds the potential to significantly improve patient outcomes. [ABSTRACT FROM AUTHOR]

Class A, rhodopsin‐like, G‐protein‐coupled receptors (GPCRs) are by far the largest class of GPCRs and are integral membrane proteins used by various cells to convert extracellular signals into intracellular responses. Initially, class A GPCRs were believed to function as monomers, but a growing body of evidence has emerged to suggest that these receptors can function as homodimers and heterodimers and can undergo functional crosstalk to influence the actions of agonists or antagonists acting at each receptor. This review will focus on the angiotensin type 1 (AT1) and type 2 (AT2) receptors, as well as the relaxin family peptide receptor 1 (RXFP1), each of which have their unique characteristics but have been demonstrated to undergo some level of interaction when appropriately co‐expressed, which influences the function of each receptor. In particular, this receptor functional crosstalk will be discussed in the context of fibrosis, the tissue scarring that results from a failed wound‐healing response to injury, and which is a hallmark of chronic disease and related organ dysfunction. LINKED ARTICLES: This article is part of a themed issue Therapeutic Targeting of G Protein‐Coupled Receptors: hot topics from the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists 2021 Virtual Annual Scientific Meeting. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.14/issuetoc [ABSTRACT FROM AUTHOR]

We tested the hypothesis that activation of angiotensin type 2 ([AT.sub.2]) receptors, by both exogenous and endogenous ANG II, modulates neurally mediated vasoconstriction in the renal cortical and medullary circulations. Under control conditions in pentobarbital-anesthetized rabbits, electrical stimulation of the renal nerves (RNS; 0.5-8 Hz) reduced renal blood flow (RBF; -88 [+ or -] 3% at 8 Hz) and cortical perfusion (CBF; -92 [+ or -] 2% at 8 Hz) more than medullary perfusion (MBF; -67 [+ or -] 6% at 8 Hz). Renal arterial infusion of ANG II, at a dose titrated to reduce RBF by ~40-50% (5-50 ng*[kg.sup.-1]*[min.sup.-]) blunted responses of MBF to RNS, without significantly affecting responses of RBF or CBF. Subsequent administration of PD 123319 (1 mg/kg plus 1 mg*[kg.sup.-1]*[h.sup.-1]) during continued renal arterial infusion of ANG II did not significantly affect responses of RBF or CBF to RNS but enhanced responses of MBF, so that they were similar to those observed under control conditions. In contrast, administration of PD 123319 alone blunted responses of CBF and MBF to RNS. Subsequent renal arterial infusion of ANG II in PD123319-pretreated rabbits restored CBF responses to RNS back to control levels. In contrast, ANG II infusion in PD123319-pretreated rabbits did not alter MBF responses to RNS. These data indicate that exogenous ANG II can blunt neurally mediated vasoconstriction in the medullary circulation through activation of [AT.sub.2] receptors. However, [AT.sub.2]-receptor activation by endogenous ANG II appears to enhance neurally mediated vasoconstriction in both the cortical and medullary circulations. kidney medulla; renal circulation; renin-angiotensin system; sympathetic nervous system

The aims of this study were to determine the contribution of the A[T.sub.2] receptor to the antihypertensive and regional vasodilatory effects of A[T.sub.1] receptor blockade in adult spontaneously hypertensive rats (SHR), 2-kidney, 1-clip hypertensive (2K1C) rats, and sham-operated normotensive rats. Several studies have provided evidence to support the notion that the A[T.sub.2] receptor may have opposing effects to those mediated by the A[T.sub.1] receptor. We therefore tested the hypothesis that the depressor and vasodilator effects of acute A[T.sub.1] receptor blockade are dependent on A[T.sub.2] receptor activation. Heart rate, mean arterial pressure, and regional hemodynamics were measured over a 4-day protocol in rats that received the following treatments in randomized order: saline vehicle, the A[T.sub.2] receptor antagonist candesartan (0.1 mg/kg iv bolus), the A[T.sub.2] receptor antagonist PD-123319 (50 [micro]g x [kg.sup.-1] x [min.sup.-1]), or both antagonists. Intravenous candesartan reduced mean arterial pressure in all groups of rats, and this was accompanied by renal and mesenteric vasodilation. Neither saline nor PD-123319 significantly affected these variables. Concomitant PD-123319 administration partially reversed the depressor and mesenteric vasodilator effects of candesartan in sham-operated normotensive rats but not in SHR or 2K1C rats. These data indicate that the A[T.sub.2] receptor contributes to the blood pressure-lowering and mesenteric vasodilator effects of A[T.sub.1] receptor blockade in the acute setting in conscious normotensive but not hypertensive rats. angiotensin receptors; candesartan; PD-123319; regional hemodynamics; hypertension; renal