Effect And Mechanism Of Long-term Low Salt Diet Induced Elevated Blood Pressure In Rat

Background:Hypertension is one of the most important risk factors for cardiovascular diseases,such as left heart failure,myocardial infarction,and renal disease.Decreasing the prevalence of hypertension may provide the greatest reduction in premature cardiovascular disease-associated deaths in the world^[1].Therefore,it is very important and urgent to further clarify the pathogenesis of hypertension and find the possible therapeutic target.Previous studies have suggested that high sodium intake can lead to cardiovascular diseases,including hypertension^[2].Moreover,salt-sensitive individuals on high salt intake are more likely to develop not only hypertension but also kidney injury related to renal inflammation and interstitial fibrosis^[3].To this end,the reduction in sodium intake is recommended to prevent cardiovascular and kidney disease,and stroke^[4].Guidelines in the treatment of hypertension include a reduction in sodium intake^[5-6].However,there are several studies showing that low sodium intake may not always be beneficial in the treatment of cardiovascular diseases^[7-13].A low sodium intake has been associated with an increased risk of cardiovascular events and death,regardless of blood pressure levels^[7,10].Some studies have found that urinary sodium excretion less than 3 g per day?presumably reflecting the sodium intake?did not decrease further the systolic blood pressure but actually tended to increase the diastolic blood pressure in subjects with or without hypertension^[11].In both normotensive and hypertensive subjects,a low sodium intake can cause insulin resistance and increase in plasma or serum renin,aldosterone,epinephrine,and norepinephrine levels^[8-10].However,there are only a few studies in humans^[14]and in animal models dealing with the increase in blood pressure caused by low salt diet^[15-17].Therefore,the present study was designed to investigate the effect of a low sodium diet?0.04%?on blood pressure and to determine the mechanisms underlying the effect of this diet in normotensive Sprague-Dawley?SD?rats.Methods:1.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.HE staining was used to observe the renal tissue structure of the two groups of rats.2.The effects on renal function of the intrarenal arterial infusion of candesartan?10?g/kg/min?,an angiotensin II receptor type 1?AT₁R?antagonist,were also measured.Plasma levels of angiotensin II were also measured.3.The contractile response of isolated mesenteric arteries was measured using a small vessel myograph.The expressions of renal AT₁R and mesenteric arterial?_1A,?_1B,and?_1DD adrenergic receptors were quantified by immunoblotting.Result:1.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.2.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.3.The expressions of?_1A and?_1D,but not?_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.