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Sodium-dependent modulation of systemic and urinary renalase expression and activity in the rat remnant kidney

Quelhas-Santos, Janetea; Sampaio-Maia, Beneditaa,b; Simões-Silva, Lilianaa; Serrão, Paulac; Fernandes-Cerqueira, Cátiaa; Soares-Silva, Isabela; Pestana, Manuela,d

Journal of Hypertension:
doi: 10.1097/HJH.0b013e32835d6e34
ORIGINAL PAPERS: Pathophysiological aspects
Abstract

Objective: The present study examined the influence of high-sodium intake on systemic and urinary renalase levels and activity in 3/4 nephrectomized (3/4nx) and Sham rats.

Results: The reduced circulating renalase levels in 3/4nx rats during normal-sodium intake were accompanied by increased plasma renalase activity. The sodium-induced increase of blood pressure in 3/4nx rats was accompanied by significant decreases in circulating renalase levels and activity as well as by a significant decrease in cardiac renalase levels in 3/4nx rats but not in Sham rats. During normal-sodium intake, no significant differences were observed in either urine renalase levels or activity between 3/4nx and Sham rats, not withstanding the ∼75% decrease in daily urine dopamine output observed in the rat remnant kidney. During high-sodium intake, urinary renalase levels increased in both 3/4nx and Sham groups by three-fold whereas urinary renalase activity increased in 3/4nx and Sham rats by greater than twelve-fold and greater than four-fold, respectively. This was accompanied by sodium-induced increases in daily urinary dopamine output in both 3/4nx and Sham rats by ∼2.3-fold and ∼1.6-fold, respectively.

Conclusion: The reduced circulating renalase levels in 3/4nx rats are accompanied by increased plasma renalase activity, which appears to be related with decreased inhibition of the circulating enzyme. Differences in systemic and urinary renalase levels and activity between 3/4nx and Sham rats during high-sodium intake may contribute to activation of the sympathetic nervous system, hypertension and enhanced cardiovascular risk in CKD but do not appear to account for the decrease in renal dopaminergic activity in the rat remnant kidney.

Author Information

aNephrology Research and Development Unit, Faculty of Medicine

bFaculty of Dental Medicine, University of Porto

cDepartment of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto

dHospital de S. João EPE, Porto, Portugal

Correspondence to Manuel Pestana, MD, PhD, Nephrology Research and Development Unit, Faculty of Medicine, University of Porto and Hospital de S. João EPE, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal. Tel: +351 22 5512100; fax: +351 22 5512228; e-mail: mvasconcelos@hsjoao.min-saude.pt

Abbreviations: 3/4nx, 3/4 nephrectomized; 3-MT, 3-metoxytyramine; CKD, chronic kidney disease; CTD, cardiomyocyte transversal diameter; DOPAC, 3,4-dihydroxyphenilacetic acid; FAD, flavin-adenine-dinucleotide; FENa+, fractional excretion of sodium; HVA, homovanillic acid; MAO-A, monoamine oxidases type A; NADH, nicotinamide adenine dinucleotide hydrogenase; Sham, sham operated

Received 5 July, 2012

Revised 27 September, 2012

Accepted 3 December, 2012

© 2013 Lippincott Williams & Wilkins, Inc.