Effects of systemic administration of kynurenic acid and glycine on renal haemodynamics and excretion in normotensive and spontaneously hypertensive rats

Bądzyńska, Bożena; Zakrocka, Izabela; Sadowski, Janusz; Turski, Waldemar A.; Kompanowska-Jezierska, Elżbieta

doi:10.1016/j.ejphar.2014.09.020

Cited by 24 publications

(11 citation statements)

References 19 publications

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“…their experiments, the authors showed that the described effects were not mediated through increased renal nerve activity [50]. Bądzyńska et al [83], supporting previous results, demonstrated that administration of glycine led to an increase of cortical renal blood flow (CBF) and total renal blood flow (RBF) in normal and in spontaneously hypertensive rats (SHR), in the absence of systemic changes in blood pressure. Furthermore, application of glycine alone caused diuresis and natriuresis, although the effect was less effective in SHR.…”

Section: Distinctive Physiological and Pathophysiological Roles Of Nmdar In The Kidneymentioning

confidence: 57%

Glutamate-Gated NMDA Receptors: Insights into the Function and Signaling in the Kidney

et al. 2020

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N-Methyl-d-aspartate receptor (NMDAR) is a glutamate-gated ionotropic receptor that intervenes in most of the excitatory synaptic transmission within the central nervous system (CNS). Aside from being broadly distributed in the CNS and having indispensable functions in the brain, NMDAR has predominant roles in many physiological and pathological processes in a wide range of non-neuronal cells and tissues. The present review outlines current knowledge and understanding of the physiological and pathophysiological functions of NMDAR in the kidney, an essential excretory and endocrine organ responsible for the whole-body homeostasis. The review also explores the recent findings regarding signaling pathways involved in NMDAR-mediated responses in the kidney. As established from diverse lines of research reviewed here, basal levels of receptor activation within the kidney are essential for the maintenance of healthy tubular and glomerular function, while a disproportionate activation can lead to a disruption of NMDAR’s downstream signaling pathways and a myriad of pathophysiological consequences.

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Section: Distinctive Physiological and Pathophysiological Roles Of Nmdar In The Kidneymentioning

confidence: 57%

Glutamate-Gated NMDA Receptors: Insights into the Function and Signaling in the Kidney

et al. 2020

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“…Moreover, KYNA is a negative allosteric modulator of the alpha 7-nicotinic receptor and an agonist of G-protein-coupled receptors as well as aryl hydrocarbon receptors (AhRs) [ 12 ]. The role of KYNA in the regulation of renal haemodynamics [ 13 ] and heart rate [ 14 ] in spontaneously hypertensive rats was recently suggested. Owing to glutamatergic and cholinergic neurotransmission modulation, the KYN pathway has been broadly explored within the context of psychiatric and neurologic disorders [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Kynurenine pathway in kidney diseases

Zakrocka

Załuska

2021

Pharmacol. Rep

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Kidney diseases have become one of the most common health care problems. Due to a growing number of advanced aged patients with concomitant disorders the prevalence of these diseases will increase over the coming decades. Despite available laboratory tests, accurate and rapid diagnosis of renal dysfunction has yet to be realized, and prognosis is uncertain. Moreover, data on diagnostic and prognostic markers in kidney diseases are lacking. The kynurenine (KYN) pathway is one of the routes of tryptophan (Trp) degradation, with biologically active substances presenting ambiguous properties. The KYN pathway is known to be highly dependent on immunological system activity. As the kidneys are one of the main organs involved in the formation, degradation and excretion of Trp end products, pathologies involving the kidneys result in KYN pathway activity disturbances. This review aims to summarize changes in the KYN pathway observed in the most common kidney disease, chronic kidney disease (CKD), with a special focus on diabetic kidney disease, acute kidney injury (AKI), glomerulonephritis and kidney graft function monitoring. Additionally, the importance of KYN pathway activity in kidney cancer pathogenesis is discussed, as are available pharmacological agents affecting KYN pathway activity in the kidney. Despite limited clinical data, the KYN pathway appears to be a promising target in the diagnosis and prognosis of kidney diseases. Modulation of KYN pathway activity by pharmacological agents should be considered in the treatment of kidney diseases.

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“…The potential direct microcirculatory effects of KYNA in the ileum are unknown, but it has been shown to increase global and cortical renal blood flow (and to improve renal excretion) under physiological conditions and to reduce renal oxidative stress during ischemia-reperfusion injury (28,29). Based on our results, some of these micro-hemodynamic effects can also be linked to a reduced ET-1 release elicited by KYNA.…”

Section: Discussionmentioning

confidence: 56%

Divergent Effects of the N-Methyl-D-Aspartate Receptor Antagonist Kynurenic Acid and the Synthetic Analog SZR-72 on Microcirculatory and Mitochondrial Dysfunction in Experimental Sepsis

et al. 2020

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Introduction: Sepsis is a dysregulated host response to infection with macro- and microhemodynamic deterioration. Kynurenic acid (KYNA) is a metabolite of the kynurenine pathway of tryptophan catabolism with pleiotropic cell-protective effects under pro-inflammatory conditions. Our aim was to investigate whether exogenously administered KYNA or the synthetic analog SZR-72 affects the microcirculation and mitochondrial function in a clinically relevant rodent model of intraabdominal sepsis.Methods: Male Sprague–Dawley rats (n = 8/group) were subjected to fecal peritonitis (0.6 g kg−1 feces ip) or a sham operation. Septic animals were treated with sterile saline or received ip KYNA or SZR-72 (160 μmol kg−1 each) 16 and 22 h after induction. Invasive monitoring was performed on anesthetized animals to evaluate respiratory, cardiovascular, renal, hepatic and metabolic dysfunctions (PaO2/FiO2 ratio, mean arterial pressure, urea, AST/ALT ratio and lactate levels, respectively) based on the Rat Organ Failure Assessment (ROFA) score. The ratio of perfused vessels (PPV) of the ileal serosa was quantified with the intravital imaging technique. Complex I- and II-linked (CI; CII) oxidative phosphorylation capacities (OXPHOS) and mitochondrial membrane potential (ΔΨmt) were evaluated by High-Resolution FluoRespirometry (O2k, Oroboros, Austria) in liver biopsies. Plasma endothelin-1 (ET-1), IL-6, intestinal nitrotyrosine (NT) and xanthine oxidoreductase (XOR) activities were measured as inflammatory markers.Results: Sepsis was characterized by an increased ROFA score (5.3 ± 1.3 vs. 1.3 ± 0.7), increased ET-1, IL-6, NT and XOR levels, and decreased serosal PPV (65 ± 12% vs. 87 ± 7%), ΔΨmt and CI–CII-linked OXPHOS (73 ± 16 vs. 158 ± 14, and 189 ± 67 vs. 328 ± 81, respectively) as compared to controls. Both KYNA and SZR-72 reduced systemic inflammatory activation; KYNA treatment decreased serosal perfusion heterogeneity, restored PPV (85 ± 11%) and complex II-linked OXPHOS (307 ± 38), whereas SZR-72 improved both CI- and CII-linked OXPHOS (CI: 117 ± 18; CII: 445 ± 107) without effects on PPV 24 h after sepsis induction.Conclusion: Treatment with SZR-72 directly modulates mitochondrial respiration, leading to improved conversion of ADP to ATP, while administration of KYNA restores microcirculatory dysfunction. The results suggest that microcirculatory and mitochondrial resuscitation with KYNA or the synthetic analog SZR-72 might be an appropriate supportive tool in sepsis therapy.

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Effects of systemic administration of kynurenic acid and glycine on renal haemodynamics and excretion in normotensive and spontaneously hypertensive rats

Cited by 24 publications

References 19 publications

Glutamate-Gated NMDA Receptors: Insights into the Function and Signaling in the Kidney

Glutamate-Gated NMDA Receptors: Insights into the Function and Signaling in the Kidney

Kynurenine pathway in kidney diseases

Divergent Effects of the N-Methyl-D-Aspartate Receptor Antagonist Kynurenic Acid and the Synthetic Analog SZR-72 on Microcirculatory and Mitochondrial Dysfunction in Experimental Sepsis

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