Key result
In hypertensive Dahl salt-sensitive rats, concomitant ARB administration (candesartan) plus a switch to a normal-salt diet normalized systolic blood pressure (138+/-8 mm Hg) and end-organ damage.
Why the study?
Does candesartan and/or dietary salt reduction improve oxidative stress, endothelial dysfunction, and hypertension in Dahl salt-sensitive rats?
Does candesartan and/or dietary salt reduction improve oxidative stress, endothelial dysfunction, and hypertension in Dahl salt-sensitive rats?
Answers are grounded in this paper and cite their sources.
In a rat model of salt-sensitive hypertension, combining an angiotensin receptor blocker with salt restriction is necessary to normalize blood pressure and reverse end-organ damage, as ARB alone only corrects oxidative stress and endothelial dysfunction.
The balance between endothelial nitric oxide (NO) and angiotensin II (Ang II) maintains the homeostasis of the cardiovascular and renal systems. We tested the hypothesis that increased oxidant stress linked to a functional imbalance between NO and Ang II might play a central pathogenetic role in salt-sensitive (SS) hypertension. We studied Dahl SS (DS) rats during the prehypertensive (5 days) and hypertensive (12 weeks) phases of a high-salt (4% NaCl) diet. Control rats received a normal-salt (0.5% NaCl, [NS]) diet. Prehypertensive DS rats (systolic blood pressure [SBP] 138+/-2 mm Hg) manifested a 35% increase (P<0.05) in aortic superoxide (O2-) production without evidence of end-organ damage. Hypertensive DS rats (SBP 214+/-11 mm Hg) had impaired endothelium-dependent relaxation (EDR) and increased aortic O2- production (320%), urinary isoprostane excretion (83%), aortic (20%) and left ventricular (LVH, 21%) hypertrophy, and proteinuria (124%). In prehypertensive DS rats, candesartan (10 mg x kg(-1) x d(-1)) an Ang II type 1 receptor blocker (ARB), normalized O2- production. In hypertensive DS rats, the ARB decreased aortic O2- production by 71% and normalized EDR without affecting SBP (212+/-8 mm Hg), aortic hypertrophy, LVH, or proteinuria. Switching hypertensive DS rats to an NS diet did not affect SBP (208+/-8 mm Hg), LVH, aortic hypertrophy, or proteinuria and had minimal effects on O2- and EDR. Concomitant ARB administration plus a switch to an NS diet normalized SBP (138+/-8 mm Hg) as well as end-organ damage. Dahl salt-resistant rats fed an HS diet for 12 weeks did not show hypertension or increased O2- production. Thus, SS hypertension might represent a specific vascular diathesis linked to functional upregulation of Ang II action (increased O2- synthesis) accompanied by insufficient NO bioavailability, which promotes severe endothelial dysfunction.
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Zhou et al. (2003) studied Salt-sensitive hypertension. Candesartan and/or normal-salt diet vs. High-salt diet (4% NaCl) control was evaluated on Aortic superoxide (O2-) production, systolic blood pressure, and end-organ damage. In hypertensive Dahl salt-sensitive rats, concomitant ARB administration (candesartan) plus a switch to a normal-salt diet normalized systolic blood pressure (138+/-8 mm Hg) and end-organ damage.
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