Abstract
Nitric oxide (NO) inhibition by high-dose NG-nitro-L-arginine methyl ester (L-NAME) is associated with several detrimental effects on the cardiovascular system. However, low-dose L-NAME increases NO synthesis, which in turn induces physiological cardiovascular benefits, probably by activating a protective negative feedback mechanism. Aerobic exercise, likewise, improves several cardiovascular functions in healthy hearts, but its effects are not known when chronically associated with low-dose L-NAME. Thus, we tested whether the association between low-dose L-NAME administration and chronic aerobic exercise promotes beneficial effects to the cardiovascular system, evaluating the cardiac remodeling process. Male Wistar rats were randomly assigned to control (C), L-NAME (L), chronic aerobic exercise (Ex), and chronic aerobic exercise associated to L-NAME (ExL). Aerobic training was performed with progressive intensity for 12 weeks; L-NAME (1.5 mg·kg-1·day-1) was administered by orogastric gavage. Low-dose L-NAME alone did not change systolic blood pressure (SBP), but ExL significantly increased SBP at week 8 with normalization after 12 weeks. Furthermore, ExL promoted the elevation of left ventricle (LV) end-diastolic pressure without the presence of cardiac hypertrophy and fibrosis. Time to 50% shortening and relaxation were reduced in ExL, suggesting a cardiomyocyte contractile improvement. In addition, the time to 50% Ca2+ peak was increased without alterations in Ca2+ amplitude and time to 50% Ca2+ decay. In conclusion, the association of chronic aerobic exercise and low-dose L-NAME prevented cardiac pathological remodeling and induced cardiomyocyte contractile function improvement; however, it did not alter myocyte affinity and sensitivity to intracellular Ca2+ handling.
Highlights
Nitric oxide (NO) is a mediator molecule that acts in multiple functions
There was no Cardiomyocyte contractility Isolated cells were placed in an experimental chamber with a glass coverslip that was base-mounted on the stage of an inverted microscope (IonOptix, USA) edge detection system with a 40Â objective lens (Nikon Eclipse – TS100, USA)
The administration of low-dose L-NAME seems to offer benefits to the cardiovascular system [6], the effects of high doses of L-NAME have been well studied as an experimental model of hypertension, and its deleterious effects are demonstrated in the literature [7,12,13,25,26]
Summary
Nitric oxide (NO) is a mediator molecule that acts in multiple functions. It was initially identified as an endotheliumderived relaxing factor and subsequently assigned to many other important biological processes [1]. It is synthesized as a free radical from L-arginine by the enzymes nitric oxide synthases (NOS). NO participates in various events, such as glucose uptake, suppression of collagen synthesis, cell growth and survival, cell contraction, and endogenous inhibition of the maladaptive cardiac hypertrophy signaling cascade [3,4,5]. Mitochondrial NOS could be involved in the regulation of cellular functions [8,9]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call