iNOS inhibition improves autonomic dysfunction and oxidative status in hypertensive obese rats

ABSTRACT

It has been suggested that nitric oxide (NO) from iNOS source is involved in inflammation and oxidative stress, and hypertension in obese subjects involves an inflammatory process. However, no study evaluated the participation of iNOS inhibition on cardiovascular, autonomic, and inflammatory parameters in obese rats. Obesity was induced by the administration of 4 mg/g body weight of monosodium glutamate (MSG) or equimolar saline (CTR) in newborn rats. On the 60th day, treatment with aminoguanidine (Amino, 50 mg/kg), an iNOS inhibitor, or 0.9% saline, was started. On the 90th day, mean arterial pressure (MAP) and heart rate (HR) were recorded in conscious rats and autonomic modulation was conducted with the CardioSeries software. Plasma samples were collected to assess lipid peroxidation and prostaglandins (PGE₂). In addition, iNOS immunohistochemistry in cardiac tissue was evaluated. MSG rats showed hypertension compared to CTR, and Amino treatment did not reverse it. Obese rats presented increased sympathetic and decreased parasympathetic modulation to the heart, reverted by Amino treatment. Plasma PGE₂ was increased in obese rats, and Amino treatment decreased. Obese rats presented increased plasma lipoperoxidation, which was decreased after Amino treatment. Also, cardiac iNOS immunohistochemistry was decreased after Amino treatment. Our data suggest that iNOS activation is involved in the systemic and cardiac mechanisms of oxidative stress, inflammation, and autonomic dysfunction derived from obesity.

KEYWORDS:

• Hypertension
• inflammation
• monosodium glutamate
• nitric oxide
• prostaglandins
• sympathetic

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Funding

This study was supported by FA (Fundação Araucária) and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), for the fellowship to Natalia Veronez da Cunha, and research fellowship to Phileno Pinge-Filho and Marli Cardoso Martins-Pinge.

Additional information

Funding

his study was supported by FA (Fundação Araucária) and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), for the fellowship to Natalia Veronez da Cunha, and research fellowship to Phileno Pinge-Filho and Marli Cardoso Martins-Pinge.