Long-term low salt diet increases blood pressure by activation of the renin-angiotensin and sympathetic nervous systems

Abstract

Background The aim of this study was to investigate the effect of long-term low salt diet on blood pressure and its underlying mechanisms.Methods Male Sprague-Dawley (SD) rats were divided into normal salt diet group (0.4%) and low salt diet group (0.04%). Blood pressure was measured with the non-invasive tail-cuff method. The contractile response of isolated mesenteric arteries was measured using a small vessel myograph. The effects on renal function of the intrarenal arterial infusion of candesartan (10 μg/kg/min), an angiotensin II receptor type 1 (AT₁R) antagonist, were also measured. The expressions of renal AT₁R and mesenteric arterial α_1A, α_1B, and α_1D adrenergic receptors were quantified by immunoblotting. Plasma levels of angiotensin II were also measured.Results Systolic blood pressure was significantly increased after 8 weeks of low salt diet. There were no obvious differences in the renal structure between the low and normal salt diet groups. However, the plasma angiotensin II levels and renal AT₁R expression were higher in low than normal salt diet group. The intrarenal arterial infusion of candesartan increased urine flow and sodium excretion to a greater extent in the low than normal salt diet group. The expressions of α_1A and α_1D, but not α_1B, adrenergic receptors, and phenylephrine-induced contraction were increased in mesenteric arteries from the low salt, relative to the normal salt diet group.Conclusion Activation of the renin-angiotensin and sympathetic nervous systems may be involved in the pathogenesis of long-term low salt diet-induced hypertension.

Keywords: Hypertension; low salt diet; renin-angiotensin system; sodium excretion; sympathetic nervous system; vascular contraction.

Figure 1.. The regulation of low salt diet on the blood pressure.

SD rats were randomly divided into low and normal salt diet groups. After 8 weeks on the diet, blood pressures were measured by a non-invasive tail-cuff manometry system. The systolic blood pressure (A) and diastolic blood pressure (B) in conscious SD rats fed with low or normal salt diet for 8 weeks are shown (*P < 0.05 vs. normal salt diet, n = 24/group).

Figure 2.. Effect of low salt diet on the renal histology.

Renal histological analysis was performed on hematoxylin and eosin-stained kidney samples from the SD rats fed low or normal salt diet for 8 weeks.

Figure 3.. Effects of low salt diet on the renin-angiotensin system.

A. Effect of low salt diet on the plasma angiotensin II (Ang II) levels. Plasma angiotensin II levels were quantified in the SD rats fed low or normal salt diet for 8 weeks (*P < 0.05 vs. normal salt diet, n = 12/group). B. Effects of low salt diet on the renal expression of AT₁R. AT₁R expression in renal cortex homogenates was quantified by immunoblotting in the SD rats fed low or normal salt diet for 8 weeks (*P < 0.05 vs. normal salt diet, n = 8/group). C and D. Effect of candesartan on urine flow and sodium excretion. The SD rats were fed low or normal salt diet for 8 weeks. Then candesartan, an AT₁R antagonist, was infused into the right renal artery via the right suprarenal artery in pentobarbital-anesthetized rats. Urine flow (C) and sodium excretion (D) were measured (*P < 0.05 vs. normal salt diet, n = 8–9). C = control, values before candesartan administration, D = values during candesartan administration, R = recovery, values after stopping the candesartan infusion.

Figure 4.. Effects of low salt diet on the sympathetic nervous system.

A. Effects of low salt diet on phenylephrine-induced contraction in mesenteric arteries. The SD rats were fed with low or normal salt diet for 8 weeks. Then, the contraction-response curves to phenylephrine (PHE, 10⁻⁹ to 10⁻⁵ M), an a₁, receptor agonist, were measured by a cumulative concentration-dependent protocol in third-order mesenteric from the SD rats fed low or normal salt diet for 8 weeks (*P < 0.05 vs. normal salt diet, n = 8/group). B. Effect of low salt diet on a₁ adrenergic receptor-mediated contraction in third order mesenteric arteries. The contractile responses to the stimulation with the α₁ adrenergic receptor agonist, phenylephrine (PHE, 10⁻⁶ M) and/or α₁ adrenergic receptor antagonist, phentolamine (PTLM, 10⁻⁶ M) were measured in third-order mesenteric from SD rats fed low or normal salt diet for 8 weeks (*P < 0.05 vs. normal salt diet, n = 12/group). C, D, and E. Effect of low salt diet on the expression of α₁ adrenergic receptors in mesenteric arteries. The expressions of α_1A, α_1B, and α_1D adrenergic receptors (AR) in mesenteric arteries were quantified by immunoblotting in the SD rats fed low or normal salt diet for 8 weeks (*P < 0.05 vs. normal salt diet, n = 8/group).