title: Modulation of Vascular ACE by Oxidative Stress in Young Syrian Cardiomyopathic Hamsters: Therapeutic Implications.
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.
authors.affiliation: Department of Physiology, University of Puerto Rico-School of Medicine, San Juan 00936, Puerto Rico. nildris.cruz@upr.edu.
authors.forename: Nildris
authors.initials: N
authors.lastname: Cruz
authors.affiliation: Department of Physiology, University of Puerto Rico-School of Medicine, San Juan 00936, Puerto Rico. jorge.miranda3@upr.edu.
authors.forename: Jorge D
authors.initials: JD
authors.lastname: Miranda
authors.affiliation: Department of Physiology, University of Puerto Rico-School of Medicine, San Juan 00936, Puerto Rico. maria.crespo3@upr.edu.|Department of Anesthesiology, University of Puerto Rico-School of Medicine, San Juan 00936, Puerto Rico. maria.crespo3@upr.edu.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Crespo
keywords: ACE; Heart failure; NOS; Syrian cardiomyopathic hamsters; endothelial dysfunction