Salt accelerates aldosterone-induced cardiac remodeling in the absence of guanylyl cyclase-A signaling.

AIMS: Excess sodium causes the development of cardiovascular diseases in conjunction with enhancing renin-angiotensin-aldosterone system (RAAS). Natriuretic peptides are sodium regulators and prevent pathological cardiac alterations by counteracting RAAS. However, it is unknown whether natriuretic peptides inhibit the sodium effect in adverse cardiac alterations. Here, we investigated whether excess salt intake could exacerbate cardiac remodeling in mice with impaired natriuretic peptide signaling. MATERIALS AND METHODS: Mice lacking the gene encoding the natriuretic peptide receptor, guanylyl cyclase-A (GC-A), and wild-type mice were administered with either a vehicle substance or a subpressor dose of aldosterone (100ng/kg/min), alongside low salt (0.001% NaCl), normal salt (0.6% NaCl), or high salt diets (6.0% NaCl) for four weeks. Mice were then sacrificed and the hearts were evaluated by histology and RT-PCR. KEY FINDINGS: Salt load did not induce cardiac changes in vehicle and aldosterone groups in wild-type mice. On the other hand, cardiac hypertrophy and interstitial fibrosis were significantly exacerbated in a salt dependent manner in GC-A knockout (KO) mice administered aldosterone, and were associated with enhanced gene expression relevant to hypertrophy, fibrosis, and oxidative stress conditions. Of note, excess salt intake increased the expression of Sgk1, serum and glucocorticoid responsive kinase-1, in aldosterone-administered GC-A KO mice. These molecular changes were not observed in wild-type mice. SIGNIFICANCE: The results of the present study demonstrate that excess salt intake induced cardiac remodeling in conjunction with aldosterone administration in GC-A KO mice, indicating that GC-A signaling attenuated the deleterious salt effect in aldosterone-induced cardiac remodeling.

Clinical significance of papillary muscle late enhancement detected via cardiac magnetic resonance imaging in patients with single old myocardial infarction.

BACKGROUND: Contrast-enhanced cardiac magnetic resonance imaging (MRI) can depict papillary muscle (PM) necrosis or fibrosis by late enhancement (LE) of PM, but its clinical significance in old myocardial infarction (OMI) has been little understood. METHODS: Myocardial LE and PM-LE were detected with contrast imaging in 60 patients with OMI caused by a single culprit coronary artery lesion. Left ventricular (LV) morphology and function, mitral valve geometry, and severity of mitral regurgitation were also evaluated by cine imaging. Sphericity index was calculated for the assessment of LV remodeling. RESULTS: PM-LE was detected in 32 of 60 (53.3%) OMI patients. Unilateral PM-LE was detected in 22 patients and bilateral PM-LE in 10 patients. Patients with bilateral PM-LE demonstrated more severe LV remodeling and functional mitral regurgitation than those with unilateral or no PM-LE (sphericity index; bilateral PM-LE, 1.60±0.15, unilateral PM-LE, 1.71±0.29, no PM-LE, 1.85±0.27, p≤0.05) (mitral regurgitation; bilateral PM-LE, 1.10±0.57, unilateral PM-LE, 0.41±0.73, no PM-LE, 0.54±0.84, p≤0.05). In cases of unilateral PM-LE, posteromedial PM-LE resulting from right coronary artery-related OMI was accompanied by less severe mitral regurgitation, while anterolateral PM-LE resulting from left coronary artery-related OMI was not associated with severity of mitral regurgitation. CONCLUSIONS: More than half of patients with OMI showed unilateral or bilateral PM-LE, and bilateral PM-LE was closely related to more severe LV remodeling and functional mitral regurgitation.