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Role of opioid signaling in kidney damage during the development of salt-induced hypertension. Life Sci Alliance 2020 12;3(12)

Date

10/14/2020

Pubmed ID

33046522

Pubmed Central ID

PMC7556751

DOI

10.26508/lsa.202000853

Scopus ID

2-s2.0-85092887222   6 Citations

Abstract

Opioid use is associated with predictors of poor cardiorenal outcomes. However, little is known about the direct impact of opioids on podocytes and renal function, especially in the context of hypertension and CKD. We hypothesize that stimulation of opioid receptors (ORs) contributes to dysregulation of intracellular calcium ([Ca2+]i) homeostasis in podocytes, thus aggravating the development of renal damage in hypertensive conditions. Herein, freshly isolated glomeruli from Dahl salt-sensitive (SS) rats and human kidneys, as well as immortalized human podocytes, were used to elucidate the contribution of specific ORs to calcium influx. Stimulation of κ-ORs, but not μ-ORs or δ-ORs, evoked a [Ca2+]i transient in podocytes, potentially through the activation of TRPC6 channels. κ-OR agonist BRL52537 was used to assess the long-term effect in SS rats fed a high-salt diet. Hypertensive rats chronically treated with BRL52537 exhibited [Ca2+]i overload in podocytes, nephrinuria, albuminuria, changes in electrolyte balance, and augmented blood pressure. These data demonstrate that the κ-OR/TRPC6 signaling directly influences podocyte calcium handling, provoking the development of kidney injury in the opioid-treated hypertensive cohort.

Author List

Golosova D, Palygin O, Bohovyk R, Klemens CA, Levchenko V, Spires DR, Isaeva E, El-Meanawy A, Staruschenko A

Authors

Ashraf El-Meanawy MD, PhD Professor in the Medicine department at Medical College of Wisconsin
Olena Isaeva PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Analgesics, Opioid
Animals
Calcium
Humans
Hypertension
Kidney
Kidney Diseases
Kidney Glomerulus
Male
Piperidines
Podocytes
Pyrrolidines
Rats
Rats, Inbred Dahl
Signal Transduction
Sodium Chloride, Dietary
TRPC Cation Channels
TRPC6 Cation Channel