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Impaired relaxation of cerebral arteries in the absence of elevated salt intake in normotensive congenic rats carrying the Dahl salt-sensitive renin gene. Am J Physiol Heart Circ Physiol 2010 Dec;299(6):H1865-74

Date

09/21/2010

Pubmed ID

20852041

Pubmed Central ID

PMC3006280

DOI

10.1152/ajpheart.00700.2010

Scopus ID

2-s2.0-78649747016   18 Citations

Abstract

This study evaluated endothelium-dependent vascular relaxation in response to acetylcholine (ACh) in isolated middle cerebral arteries (MCA) from Dahl salt-sensitive (Dahl SS) rats and three different congenic strains that contain a portion of Brown Norway (BN) chromosome 13 introgressed onto the Dahl SS genetic background through marker-assisted breeding. Two of the congenic strains carry a 3.5-Mbp portion and a 2.6-Mbp portion of chromosome 13 that lie on opposite sides of the renin locus, while the third contains a 2.0-Mbp overlapping region that includes the BN renin allele. While maintained on a normal salt (0.4% NaCl) diet, MCAs from Dahl SS rats and the congenic strains retaining the Dahl SS renin allele failed to dilate in response to ACh, whereas MCAs from the congenic strain carrying the BN renin allele exhibited normal vascular relaxation. In congenic rats receiving the BN renin allele, vasodilator responses to ACh were eliminated by nitric oxide synthase inhibition with N(G)-nitro-l-arginine methyl ester, angiotensin-converting enzyme inhibition with captopril, and AT(1) receptor blockade with losartan. N(G)-nitro-l-arginine methyl ester-sensitive vasodilation in response to ACh was restored in MCAs of Dahl SS rats that received either a 3-day infusion of a subpressor dose of angiotensin II (3 ng·kg(-1)·min(-1) iv), or chronic treatment with the superoxide dismutase mimetic tempol (15 mg·kg(-1)·day(-1)). These findings indicate that the presence of the Dahl SS renin allele plays a crucial role in endothelial dysfunction present in the cerebral circulation of the Dahl SS rat, even in the absence of elevated dietary salt intake, and that introgression of the BN renin allele rescues endothelium-dependent vasodilator responses by restoring normal activation of the renin-angiotensin system.

Author List

Durand MJ, Moreno C, Greene AS, Lombard JH

Authors

Matt Durand PhD Associate Professor in the Physical Medicine and Rehabilitation department at Medical College of Wisconsin
Julian H. Lombard PhD Professor in the Physiology department at Medical College of Wisconsin




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

Acetylcholine
Angiotensin II
Angiotensin II Type 1 Receptor Blockers
Angiotensin-Converting Enzyme Inhibitors
Animals
Animals, Congenic
Antioxidants
Blood Pressure
Captopril
Crosses, Genetic
Cyclic N-Oxides
Dose-Response Relationship, Drug
Enzyme Inhibitors
Infusions, Intravenous
Losartan
Male
Middle Cerebral Artery
NG-Nitroarginine Methyl Ester
Nitric Oxide
Rats
Rats, Inbred BN
Rats, Inbred Dahl
Renin
Renin-Angiotensin System
Sodium Chloride, Dietary
Spin Labels
Superoxides
Vasodilation
Vasodilator Agents