Abstract
Increased vascular angiotensin-converting enzyme (ACE) activity and oxidative stress are present in young Syrian cardiomyopathic hamsters (SCH) before the clinical manifestation of heart failure (HF). The developmental time-course of these alterations and their potential interactions, however, are still unknown. We evaluated mRNA and protein levels of ACE, endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS) in the vasculature of SCH from one to four months of age. Total RNA and proteins were quantified with real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot, respectively. The role of nitric oxide (NO) on vascular ACE activity was also assessed. ACE mRNA and protein levels were up-regulated in SCH at two months of age compared with controls (CT) (p < 0.05). At this two-month stage, eNOS protein levels were lower in SCH (87%) than in CT (100%) (p < 0.05), although iNOS protein levels increased significantly (482%) compared to CT (100%; p < 0.05). In addition, ACE mRNA expression and activity were modulated by NO at two months of age. Thus, the combination of low eNOS and high iNOS protein levels may underlie vascular renin-angiotensin system (RAS) over-activation. Altogether, these factors may contribute to the development of endothelial dysfunction and vascular hyper-reactivity in the early stages of heart failure, and eventually trigger cardiac deterioration in this animal model of HF.
Highlights
Heart failure (HF) is a complex syndrome in which the capacity of the heart to pump blood is decreased, leading to a mismatch between cardiac output and the metabolic demands of tissues. the precise mechanisms involved in the etiology of HF remain unclear, over-activation of the renin-angiotensin system (RAS) and the sympathetic nervous system is a known hallmark of this condition [1]
The precise mechanisms involved in the etiology of HF remain unclear, over-activation of the renin-angiotensin system (RAS) and the sympathetic nervous system is a known hallmark of this condition [1]
Syrian cardiomyopathic hamsters (SCH) is secondary to the over-activation of RAS that results from reduced nitric oxide (NO) bioavailability
Summary
Heart failure (HF) is a complex syndrome in which the capacity of the heart to pump blood is decreased, leading to a mismatch between cardiac output and the metabolic demands of tissues. The precise mechanisms involved in the etiology of HF remain unclear, over-activation of the renin-angiotensin system (RAS) and the sympathetic nervous system is a known hallmark of this condition [1]. Endothelial dysfunction and oxidative stress are commonly found in HF [2]. Endothelial dysfunction, which is characterized by an impaired ability of acetylcholine to relax blood vessels, may result from either a decrease in nitric oxide (NO) bioavailability or its production, or both [3]. Increased angiotensin II levels may reduce NO bioavailability by activating NADPH oxidase, thereby favoring the production of reactive oxygen species (ROS), which are NO scavengers [4]
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