Introgression of the Brown Norway renin allele rescued endothelium-dependent vasodilator responses to acetylcholine in cerebral arteries of normotensive Dahl salt-sensitive rats on a normal salt diet.
The Dahl SS renin allele contributes to cerebral endothelial dysfunction even in the absence of high salt intake, a defect that can be rescued by introgressing the BN renin allele or restoring normal renin-angiotensin system activation.
p-value: p=<0.05
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.
Durand et al. (Sat,) conducted a other in Endothelial dysfunction in salt-sensitive hypertension model. Introgression of Brown Norway (BN) renin allele (Ren1-BN strain) vs. Dahl SS renin allele (Dahl SS, Ren1-SSA, Ren1-SSB strains) was evaluated on Vasodilator response to acetylcholine (ACh) in isolated middle cerebral arteries (p=<0.05). Introgression of the Brown Norway renin allele rescued endothelium-dependent vasodilator responses to acetylcholine in cerebral arteries of normotensive Dahl salt-sensitive rats on a normal salt diet.