Cardiorenal abnormalities associated with high sodium intake: correction by spironolactone in rats

Abstract

Cordaillat, Magali, Caroline Rugale, Daniel Casellas, Albert Mimran, and Bernard Jover. Cardiorenal abnormalities associated with high sodium intake: correction by spironolactone in rats. Am J Physiol Regul Integr Comp Physiol 289: R1137-R1143, 2005. First published May 26, 2005; doi:10.1152/ajpregu.00154.2005.-Reversal by the mineralocorticoid receptor antagonist spironolactone on cardiac and renal abnormalities, associated with long-term (since weaning) administration of a high (2 and 8% NaCl chow, HS2 and HS8) sodium diet, was assessed in Sprague-Dawley rats. At the age of 5 mo, spironolactone (20 or 100 mg/kg, gavage) or placebo were given for 14 days to HS2 and HS8 rats. A group fed a regular diet (0.8% NaCl, NS) remained untreated. High sodium intake had no detectable effect on blood pressure; however, cardiac mass index and cross-sectional area of the carotid artery, as well as albuminuria, were increased only in the HS8 group compared with the control group on NS diet. In addition, a marked reduction in glomerular filtration rate (by 40%), associated with a nonproportional fall in renal plasma flow (thus resulting in a decrease in filtration fraction), was observed only in the HS8 group. No change in cardiac and renal fibrosis was detected. Production of the reactive oxygen species (ROS) by aortic tissue was increased in HS8 rats, whereas ROS production by the heart was unaffected. Only the high dose of spironolactone was effective, as it markedly reversed the cardiac hypertrophy and renal hypofiltration associated with the HS8 feeding. The changes were observed in the absence of any effect on systemic blood pressure and production of ROS. These observations favor aldosterone's role in the deleterious effects of marked and prolonged increases in sodium intake. spironolactone; renal function; reactive oxygen species; cardiac hypertrophy IN ADDITION TO ITS WIDELY debated effect on blood pressure, chronic variation of sodium intake has been reported to modulate the cardiovascular morphology in human and experimental models. In animal studies, dietary sodium restriction has been shown to prevent the development of cardiac hypertrophy in renovascular (13) and ANG II-induced hypertension (14), independently of blood pressure. Reversal of cardiac hypertrophy was achieved by 6 wk on a low-sodium diet in 2-kidney, one-clip hypertensive rats (17). Administration of a diet containing 8% sodium chloride for more than 4 wk was associated with the development of left ventricular hypertrophy, cardiac fibrosis, and an increase in collagen content (10,23).Because an increase in systemic pressure associated with high sodium was not consistently observed, it was suggested that a direct effect of sodium may underlie the increased sensitivity of target organs to blood pressure. Interestingly, in a cohort of normotensive subjects and never-treated patients with essential hypertension, it was recently demonstrated that increasing dietary sodium (as estimated by 24-h natriuresis), enhanced the slope of the relationship between...

Nitric oxide pathway counteracts enhanced contraction to membrane depolarization in aortic rings of rats on high-sodium diet

“…In the current study, HS diet caused no significant increase in blood pressure. This observation confirms our previous report (7) and is in agreement with observations made with similar (22) or a shorter (10) period of HS feeding. In addition, no aortic hypertrophy was detected in the present HS rats, as previously shown on the carotid artery of a 4-mo-old rat on 2% NaCl diet for 6 mo (25).…”

“…Fifty weanling male Sprague-Dawley rats were randomly assigned to two groups of 25 animals and fed NS or HS diet containing 0.8 or 8% NaCl, respectively, as previously described (7). After 18 -20 wk i.e., at 5 mo of age, arterial pressure was measured in the carotid artery of the anesthetized animal (pentobarbital sodium, 50 mg/kg body wt ip; Sanofi), and rats were prepared for the aortic reactivity study.…”

“…In a previous study, feeding weanling rats with an 8% NaCl diet for 4 mo was devoid of major effect on arterial pressure, and it was accompanied by a cardiac and carotid artery hypertrophy (7). Facing the salt loading, change in vascular reactivity may be one of the factors involved in the lack of hypertension observed in the latter model.…”

Angiotensin Blockade Prevents Salt-Induced Injury of the Renal Circulation in Spontaneously Hypertensive Rats

“…However, experimental studies have demonstrated local participation of the RAAS in cardiac [31], vascular [29], and kidney tissue [32,33,34], suggesting that despite systemic suppression of the juxtaglomerular RAAS with salt loading, locally generated cardiac and renal RAAS may be stimulated by salt loading [30]. Thus, improvements of proteinuria and renal hemodynamics after aldosterone inhibition [35] have been reported in salt-loaded rats, unrelated to arterial pressure changes. Furthermore, the transforming growth factor-β1 has also been implicated as an important factor for mediating the development of cardiac and renal fibrosis associated with salt loading, since overexpression of transforming growth factor-β1 has been reported in studies with salt-loaded rats [36].…”

Dietary Sodium, Aldosterone, and Left Ventricular Mass Changes During Long-Term Inhibition of the Renin-Angiotensin System

“…34 The demonstration of a role for aldosterone was reinforced by the observation that cardiac and renal abnormalities induced by long-term high sodium diet were corrected by spironolactone given during the last week of the study period. 20 In humans, evidence that dietary sodium impacts the effects of aldosterone is sparse. In a cross-sectional study conducted in 317 untreated subjects, Jin et al 17 observed that LVM increased with sodium intake (estimated as 24-hour natriuresis) and was positively associated with urinary aldosterone (a better estimate of tissue exposure to aldosterone than plasma aldosterone).…”