Nitric Oxide Alleviated High Salt-Induced Cardiomyocyte Apoptosis and Autophagy Independent of Blood Pressure in Rats

Area of Science:

• Cardiovascular Science
• Molecular Biology
• Cellular Biology

Background:

• High-salt diet (HSD) is linked to cardiovascular disease.
• The direct impact of HSD on cardiac damage, independent of blood pressure, requires further investigation.
• The role of nitric oxide (NO) in mitigating HSD-induced cardiac cellular stress is not fully understood.

Purpose of the Study:

• To determine if HSD induces cardiac damage independently of blood pressure.
• To investigate the effect of NO on high-salt-induced cardiomyocyte apoptosis and autophagy.

Main Methods:

• Rats were subjected to an 8% HSD.
• H9C2 cells and primary neonatal rat cardiomyocytes (NRCM) were treated with sodium chloride (NaCl) in vitro.
• Levels of apoptosis markers (cleaved-caspase 3/8, Bax/Bcl2) and autophagy markers (LC3 II/I, Beclin-1, ATG7) were measured.
• Nitric oxide donor sodium nitroprusside (SNP) was used to assess NO's protective effects.

Main Results:

• HSD increased cardiac apoptosis and autophagy markers in rats, irrespective of hypertension status.
• NaCl treatment elevated apoptosis and autophagy markers in H9C2 cells and NRCM.
• NO levels were reduced in HSD rats, while eNOS expression was altered.
• SNP administration reversed NaCl-induced apoptosis and autophagy in vitro and in vivo, without affecting blood pressure in hypertension-resistant rats.

Conclusions:

• High-salt diet promotes cardiac damage and cellular stress (apoptosis and autophagy) independently of elevated blood pressure.
• Exogenous nitric oxide supplementation can effectively alleviate high-salt-induced cardiomyocyte apoptosis and autophagy.
• These findings highlight NO's potential therapeutic role in managing salt-induced cardiac pathology.