High-sodium intake aggravates myocardial injuries induced by aldosterone via oxidative stress in Sprague-Dawley rats

Abstract

Aim: To evaluate the effects of aldosterone with or without high sodium intake on blood pressure, myocardial structure and left ventricular function in rats, and to investigate the mechanisms underlying the effects. Methods: Eight-week-old male Sprague-Dawley rats were randomly divided into 3 groups: (1) control (CON) group fed a normal sodium diet, (2) aldosterone (ALD) group receiving aldosterone infusion and a normal sodium diet, and (3) high sodium plus aldosterone (HS-ALD) group receiving 1% NaCl diet in conjunction with aldosterone infusion. Aldosterone was administered through continuously subcutaneous infusion with osmotic minipump at the rate of 0.75 μg/h for 8 weeks. The myocardium structure was observed using transthoracic echocardiography and transmission electron microscopy. The collagen deposition in left ventricle was evaluated with Masson's trichrome staining. The expression of IL-18, p22phox, and p47phox proteins was examined using Western blot analysis. Results: The systolic blood pressure in the ALD and HS-ALD groups was significantly higher than that in the CON group after 2-week treatment. But the blood pressure showed no significant difference between the HS-ALD and ALD groups. The left ventricular hypertrophy, myocardial collagen deposition and oxidative stress were predominantly found in the HS-ALD and ALD group. Furthermore, the breakdown of myocardial structure and oxidative stress were more apparent in the HS-ALD group as compared with those in the ALD group. Conclusion: Long-term infusion of aldosterone results in hypertension and profibrotic cardiovascular responses in rats fed a normal sodium diet, which were mediated by oxidative stress. High-sodium intake could aggravate myocardial injuries induced by aldosterone.

Mitochondrial reactive oxygen species-mediated NLRP3 inflammasome activation contributes to aldosterone-induced renal tubular cells injury

“…IL-1β and IL-18 are two inflammatory cytokines implicated in various kinds of CKD, and several studies demonstrated that IL-1β and IL-18 could induce expression of mesenchymal markers in tubular epithelial cells [ 25 , 26 ]. It has also been demonstrated that IL-1β and IL-18 are significantly increased in Aldo-induced renal inflammation and fibrosis in vivo [ 27 , 28 ], suggesting that IL-1β and IL-18 may be the key mediators of Aldo-induced renal injury, although the exact mechanisms remained unclear. In present study, we demonstrate that Aldo stimulation induces the production of mature IL-1β/IL-18 in renal tubular cells in a dose- and time-dependent manner.…”

Rotenone Attenuates Renal Injury in Aldosterone-Infused Rats by Inhibiting Oxidative Stress, Mitochondrial Dysfunction, and Inflammasome Activation

“…Activated NLRP3 inflammasome then promotes tissue injury by upregulating pro-inflammatory cytokines IL-18 and IL-1β [ 6 ]. Previous studies have reported markedly elevated IL-18 and IL-1β levels in Aldo-induced renal inflammation and fibrosis in vivo [ 7 , 8 ]. Our previous work also suggests that reactive oxygen species (ROS) participate in Aldo-induced renal injury [ 9 ].…”

Associations Between Metabolic Profiles and Target-Organ Damage in Chinese Individuals With Primary Aldosteronism

“…Consistent with previous studies (4,23), our study showed that compared to matched EH controls, PA patients exhibited more renal damage indicated by reduced eGFR and greater prevalence of microalbuminuria, as well as more cardiac damage indicated by an increased prevalence of LVH. On the one hand, there is accumulating evidence including our previous researches, which support that many detrimental effects of aldosterone excess are involved in causing pre-clinical TOD in the PA patients; they include inflammation, oxidative stress, endothelial dysfunctions, and vascular calcification (7,(24)(25)(26)(27). On the other hand, a majority of patients with MetS, a cluster of risk factors, tend to develop structural and functional abnormalities of target organs, which precede cardiovascular complications (28,29).…”