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Amelioration of salt-induced vascular dysfunction in mesenteric arteries of Dahl salt-sensitive rats by missense mutation of extracellular superoxide dismutase. Am J Physiol Heart Circ Physiol 2014 Feb;306(3):H339-47 PMID: 24322611 PMCID: PMC3920146

Pubmed ID

24322611

DOI

10.1152/ajpheart.00619.2012

Abstract

Superoxide dismutase (SOD) enzymes, including extracellular SOD (ecSOD), are important for scavenging superoxide radicals (O2(·-)) in the vasculature. This study investigated vascular control in rats [SS-Sod(3m1Mcwi) (ecSOD(E124D))] with a missense mutation that alters a single amino acid (E124D) of ecSOD that produces a malfunctioning protein in the salt-sensitive (Dahl SS) genetic background. We hypothesized that this mutation would exacerbate endothelial dysfunction due to elevated vascular O2(·-) levels in SS, even under normal salt (NS; 0.4% NaCl) conditions. Aortas of ecSOD(E124D) rats fed standard rodent chow showed enhanced sensitivity to phenylephrine and reduced relaxation to acetylcholine (ACh) vs. SS rats. Endothelium-dependent dilation to ACh was unaffected by the mutation in small mesenteric arteries of ecSOD(E124D) rats fed NS diet, and mesenteric arteries of ecSOD(E124D) rats were protected from endothelial dysfunction during short-term (3-5 days) high-salt (HS; 4% NaCl) diet. ACh-induced dilation of mesenteric arteries of ecSOD(E124D) rats and SS rats fed NS diet was inhibited by N(G)-nitro-l-arginine methyl ester and/or by H2O2 scavenging with polyethylene glycol-catalase at higher concentrations of ACh. Total SOD activity was significantly higher in ecSOD(E124D) rats vs. SS controls fed HS diet, most likely reflecting a compensatory response to loss of a functional ecSOD isoform. These findings indicate that, contrary to its effect in the aorta, this missense mutation of ecSOD in the SS rat genome has no negative effect on vascular function in small resistance arteries, but instead protects against salt-induced endothelial dysfunction, most likely via compensatory mechanisms involving an increase in total SOD activity.

Author List

Beyer AM, Raffai G, Weinberg BD, Fredrich K, Rodgers MS, Geurts AM, Jacob HJ, Dwinell MR, Lombard JH

Authors

Andreas M. Beyer PhD Associate Professor in the Medicine department at Medical College of Wisconsin
Melinda R. Dwinell PhD Center Associate Director, Associate Professor in the Physiology department at Medical College of Wisconsin
Aron Geurts PhD Associate Professor in the Physiology department at Medical College of Wisconsin
Julian H. Lombard PhD Professor in the Physiology department at Medical College of Wisconsin




Scopus

2-s2.0-84893409421   4 Citations

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

Acetylcholine
Animals
Aorta
Catalase
Mesenteric Arteries
Mutation, Missense
NG-Nitroarginine Methyl Ester
Oxygen
Phenylephrine
Polyethylene Glycols
Rats, Inbred Dahl
Sodium Chloride, Dietary
Superoxide Dismutase
Vasodilation
jenkins-FCD Prod-331 a335b1a6d1e9c32173c9534e6f6ff51494143916