Abstract
Type 2 diabetes mellitus (T2DM) is associated with risk for chronic kidney disease (CKD), which is associated with a decrease in renal myogenic tone - part of renal autoregulatory mechanisms. Novel class of drugs used for the treatment of T2DM, dipeptidyl peptidase-4 (DPP-4) inhibitors, have protective effects on the cardiovascular system. A Zucker Diabetic Fatty (ZDF) rat is an animal model of T2DM that displays progressive nephropathy in which inflammation leads to initiation of renal fibrosis and CKD. We hypothesized that CKD in the ZDF rat is related to decrease in myogenic constriction (MC) of intrarenal arteries and that treatment with the DPP-4 inhibitor, vildagliptin, prevents such changes. Renal arteries isolated from 25 weeks old lean, ZDF and ZDF treated with vildagliptin (n=7 in each group) were transferred to an arteriograph to assess agonist and pressure induced contractile responses. Furthermore, blood glucose, proteinuria, focal glomerulosclerosis (FGS) and p22phox mRNA expression of renal tissue were measured. Compared to lean controls, ZDF had significantly increased plasma glucose and cholesterol levels, focal glomerulosclerosis and interstitial α-SMA expression, and urinary protein excretion. ZDF rats also had impaired MC of renal arteries and increased renal p22phox expression. Vildagliptin did not affect plasma glucose levels or proteinuria, but effectively decreased glomerulosclerosis and restored MC and p22phox expression to the levels found in lean rats. Based on these data, it can be suggested that vildagliptin treatment protects diabetic rats from the loss of renal vascular reactivity and the development of glomerulosclerosis perhaps secondary to a reduction in oxidative stress.
Keywords: Chronic kidney disease, DPP-IV inhibitors, glomerulosclerosis, glucagon-like peptide-1, myogenic constriction, oxidative stress, type 2 diabetes melitus, ZDF rat.
Current Vascular Pharmacology
Title:Vildagliptin Restores Renal Myogenic Function and Attenuates Renal Sclerosis Independently of Effects on Blood Glucose or Proteinuria in Zucker Diabetic Fatty Rat
Volume: 12 Issue: 6
Author(s): Peter Vavrinec, Robert H. Henning, Sjoerd W. Landheer, Yumei Wang, Leo E. Deelman, Richard P.E. van Dokkum and Hendrik Buikema
Affiliation:
Keywords: Chronic kidney disease, DPP-IV inhibitors, glomerulosclerosis, glucagon-like peptide-1, myogenic constriction, oxidative stress, type 2 diabetes melitus, ZDF rat.
Abstract: Type 2 diabetes mellitus (T2DM) is associated with risk for chronic kidney disease (CKD), which is associated with a decrease in renal myogenic tone - part of renal autoregulatory mechanisms. Novel class of drugs used for the treatment of T2DM, dipeptidyl peptidase-4 (DPP-4) inhibitors, have protective effects on the cardiovascular system. A Zucker Diabetic Fatty (ZDF) rat is an animal model of T2DM that displays progressive nephropathy in which inflammation leads to initiation of renal fibrosis and CKD. We hypothesized that CKD in the ZDF rat is related to decrease in myogenic constriction (MC) of intrarenal arteries and that treatment with the DPP-4 inhibitor, vildagliptin, prevents such changes. Renal arteries isolated from 25 weeks old lean, ZDF and ZDF treated with vildagliptin (n=7 in each group) were transferred to an arteriograph to assess agonist and pressure induced contractile responses. Furthermore, blood glucose, proteinuria, focal glomerulosclerosis (FGS) and p22phox mRNA expression of renal tissue were measured. Compared to lean controls, ZDF had significantly increased plasma glucose and cholesterol levels, focal glomerulosclerosis and interstitial α-SMA expression, and urinary protein excretion. ZDF rats also had impaired MC of renal arteries and increased renal p22phox expression. Vildagliptin did not affect plasma glucose levels or proteinuria, but effectively decreased glomerulosclerosis and restored MC and p22phox expression to the levels found in lean rats. Based on these data, it can be suggested that vildagliptin treatment protects diabetic rats from the loss of renal vascular reactivity and the development of glomerulosclerosis perhaps secondary to a reduction in oxidative stress.
Export Options
About this article
Cite this article as:
Vavrinec Peter, Henning H. Robert, Landheer W. Sjoerd, Wang Yumei, Deelman E. Leo, Dokkum P.E. van Richard and Buikema Hendrik, Vildagliptin Restores Renal Myogenic Function and Attenuates Renal Sclerosis Independently of Effects on Blood Glucose or Proteinuria in Zucker Diabetic Fatty Rat, Current Vascular Pharmacology 2014; 12 (6) . https://dx.doi.org/10.2174/15701611113116660151
DOI https://dx.doi.org/10.2174/15701611113116660151 |
Print ISSN 1570-1611 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6212 |
Call for Papers in Thematic Issues
Advancements in Arterial Stiffness: Novel Therapeutic Frontiers
Arterial stiffness, a hallmark of cardiovascular disease, poses significant challenges in contemporary healthcare. This thematic issue delves into the multifaceted landscape of arterial stiffness and explores cutting-edge therapeutic interventions aimed at mitigating its adverse effects. Within these pages, readers will find a comprehensive overview of the mechanisms underlying arterial stiffness, ...read more
Ischemic Cardiovascular Diseases: Mechanisms, Diagnosis and Therapy
Ischemic cardiovascular disease includes myocardial infarction, coronary atherosclerotic heart disease, angina pectoris, etc., constitute the leading cause of patient mortality by preventing tissues from getting sufficient oxygen and nutrients. Ischemic heart disease, as a clinical condition, is characterized by myocardial ischemia, causing an imbalance between myocardial blood supply and demand, ...read more
TREATMENT OF CARDIOVASCULAR DISEASE IN CHRONIC AND END STAGE KIDNEY DISEASE
Cardiovascular disease still remains the leading cause of death in Chronic and End Stage Kidney Disease, accounting for more than half of all deaths in dialysis patients. During the past decade, research has been focused on novel therapeutic agents that might delay or even reverse cardiovascular disease and vascular calcification, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Platelet Activation in Atherogenesis Associated with Low-Grade Inflammation
Inflammation & Allergy - Drug Targets (Discontinued) Benign Prostatic Hyperplasia and Clinical Prostate Cancer - Two New Components of the Metabolic Syndrome
Current Hypertension Reviews Therapeutic Potential of High Mobility Group Box-1 in Ischemic Injury and Tissue Regeneration
Current Vascular Pharmacology Having a Promising Efficacy on Type II Diabetes, It’s Definitely a Green Tea Time
Current Medicinal Chemistry IGF-1R Inhibitor Ameliorates Diabetic Nephropathy with Suppressed HMGN1/TLR4 Pathway
Endocrine, Metabolic & Immune Disorders - Drug Targets Polymorphism rs9939609 of Fat Mass and Obesity-associated Gene Correlation with Leptin Level of Obese Women Suffered from Type 2 Diabetes
Current Diabetes Reviews Telmisartan in the Management of Diabetic Nephropathy: A Contemporary View
Current Diabetes Reviews SGLT-2 Inhibitors in Type 1 Diabetes Mellitus: A Comprehensive Review of the Literature
Current Clinical Pharmacology Erythropoietin Employs Cell Longevity Pathways of SIRT1 to Foster Endothelial Vascular Integrity During Oxidant Stress
Current Neurovascular Research Mitochondrial Deficits Accompany Cognitive Decline Following Single Bilateral Intracerebroventricular Streptozotocin
Current Alzheimer Research Functional Genomics of the Oxidative Stress Pathway
Current Hypertension Reviews Use of Double-source Computed Tomography for Evaluation of the Relationship Between Smoking and Coronary Plaques
Current Medical Imaging subject Index To Volume 4
Combinatorial Chemistry & High Throughput Screening Polyphenols-Rich Natural Products for Treatment of Diabetes
Current Medicinal Chemistry Impact of Mitochondrial Toxicity of HIV-1 Antiretroviral Drugs on Lipodystrophy and Metabolic Dysregulation
Current Pharmaceutical Design Subject Index To Volume 7
Current Drug Targets Structural and Functional Characterization of Pathogenic Non- Synonymous Genetic Mutations of Human Insulin-Degrading Enzyme by In Silico Methods
CNS & Neurological Disorders - Drug Targets Modulators of Networks: Molecular Targets of Arterial Calcification Identified in Man and Mice
Current Pharmaceutical Design Pharmacotherapy of Schizophrenia: The Past, Present and Future
Current Drug Therapy Decrease in Serum Levels of Adiponectin and Increase in 8-OHdG: a Culprit for Cognitive Impairment in the Elderly Patients with Type 2 Diabetes
Current Molecular Medicine