Faculty Collaboration Database

Introgression of the Brown Norway renin allele onto the Dahl salt-sensitive genetic background increases Cu/Zn SOD expression in cerebral arteries. Am J Hypertens 2011 May;24(5):563-8

Date

02/19/2011

Pubmed ID

21331057

Pubmed Central ID

PMC3285562

DOI

10.1038/ajh.2011.15

Scopus ID

2-s2.0-79954754567 (requires institutional sign-in at Scopus site)   16 Citations

Abstract

BACKGROUND: Nitric oxide (NO)-dependent vasodilation is impaired in middle cerebral arteries (MCAs) from Dahl salt-sensitive (SS) rats that are fed normal salt (NS) diet, due to low plasma renin activity and chronic exposure to low plasma angiotensin II (ANG II) levels. NO-dependent vasodilator responses are rescued in MCAs from Ren1-BN congenic rats, which have a 2.0 Mbp portion of Brown Norway (BN) chromosome 13 containing the renin gene introgressed onto the Dahl SS genetic background.

METHODS: Vascular superoxide levels were measured with dihydroethidium (DHE) fluorescence in basilar arteries from 10- to 14-week-old, male Dahl SS and Ren1-BN congenic rats that fed NS diet. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and xanthine oxidase (XO) activity were also measured in cerebral artery tissue homogenates. Expression of the superoxide dismutase (SOD) enzymes was evaluated via western blotting in cerebral arteries from the two rat strains.

RESULTS: Superoxide levels were significantly higher in basilar arteries from Dahl SS rats compared to Ren1-BN congenic rats. NADPH oxidase and XO activity were similar between the two rat strains. Cu/Zn SOD expression was significantly higher in cerebral arteries from Ren1-BN congenic rats vs. those from Dahl SS rats. The expression of Mn-SOD was similar in cerebral arteries from both strains.

CONCLUSIONS: These findings suggest that introgressing the BN renin allele onto the Dahl SS genetic background to restore normal activity of the renin-angiotensin system (RAS) protects NO-dependent vascular relaxation in cerebral arteries by increasing the expression of Cu/Zn SOD and lowering vascular superoxide levels.

Author List

Durand MJ, Lombard JH

Author

Matt Durand PhD Associate Professor in the Physical Medicine and Rehabilitation department at Medical College of Wisconsin

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

Alleles
Animals
Cerebral Arteries
Male
NADPH Oxidases
Nitric Oxide
Rats
Rats, Inbred BN
Rats, Inbred Dahl
Renin
Superoxide Dismutase
Superoxides
Xanthine Oxidase