The Positive Functional and Structural Cardiovascular Impact of Homoarginine in Aged Rats Via Modulation of Cardiac iNOS/Fibrosis Pathway and AMPK

Abstract

Objectives To investigate the cardiovascular protective effect of HA in aged rats and to clarify the underlying mechanisms. Background: Aging is a natural process, which has a gradual biological impact on the normal functions of different organs. Methods Thirty male Wistar rats were divided in to 3 groups: adult (4-6 months), aged (23-24 months) and aged HA supplemented groups. Systolic blood pressure (SBP), electrocardiogram (ECG) and aortic blood flow parameters were recorded for all rats. Then, rats were sacrificed and cardiac tissue was dissected to measure the cardiac levels of malondialdehyde (MDA), superoxide dismutase (SOD) and tumor necrosis factor-α (TNF-α). Also, cardiac tissues were fixed for histological and immunohistochemical (IHC) studies. Results The aged group showed significant increase in SBP, aortic resistance parameter (RP), cardiac TNF-α and MDA, but significant decrease in aortic mean velocity (MNV), heart rate (HR), R wave amplitude and cardiac SOD with apparent collagen deposition between the degenerated cardiomyocytes, compared to adult rats. Moreover, the IHC revealed significant increase in the intensity of inducible nitric oxide synthase (iNOS) and significant decrease in desmin and adenosine monophosphate-activated protein kinase (AMPK) intensities. Fortunately, HA supplementation improved the measured parameters in aged rats. Conclusion HA might improve the aging induced cardiovascular changes by down-regulation of iNOS/fibrosis pathway and upregulation of desmin and AMPK in cardiac tissues.