Calorie Restriction Attenuates Monocrotaline-induced Pulmonary Arterial Hypertension in Rats

Abstract

Abstract:Calorie restriction (CR) is one of the most effective nonpharmacological interventions protecting against cardiovascular disease, such as hypertension in the systemic circulation. However, whether CR could attenuate pulmonary arterial hypertension (PAH) is largely unknown. The PAH model was developed by subjecting the rats to a single subcutaneous injection of monocrotaline. CR lowered mean pulmonary arterial pressure (mPAP) and reduced vascular remodeling and right ventricular hypertrophy in PAH rats. Meanwhile, CR attenuated endothelial dysfunction as evidenced by increased relaxation in response to acetylcholine. The beneficial effects of CR were associated with restored sirtuin-1 (SIRT1) expression and endothelial nitric oxide synthase (eNOS) phosphorylation and reduced eNOS acetylation in pulmonary arteries of PAH rats. To further clarify the role of SIRT1 in the protective effects of CR, adenoviral vectors for overexpression of SIRT1 were administered intratracheally at 1 day before monocrotaline injection. Overexpression of SIRT1 exhibited similar beneficial effects on mPAP and endothelial function, and increased eNOS phosphorylation and reduced eNOS acetylation in the absence of CR. Moreover, SIRT1 overexpression attenuated the increase in mPAP in hypoxia-induced PAH animals. Overall, the present data demonstrate that CR may serve as an effective treatment of PAH, and targeting the SIRT1/eNOS pathway may improve treatment of PAH.

Lower Body Weight in Rats Under Hypobaric Hypoxia Exposure Would Lead to Reduced Right Ventricular Hypertrophy and Increased AMPK Activation

“…Given that we cannot correlate both proteins (AMPK and mTOR) with the actual degree of PAP at any stage, this would be a limitation. However, in that sense, the literature supports and describes that CR could decrease PAP and RVH (Ding et al, 2015). Thence, in the current study, it is clear that with CR, and the hypoxia regimen increased the AMPK activity and inhibited mTOR, which might explain the RVH that was found.…”

SIRT1 protects against myocardial ischemia–reperfusion injury via activating eNOS in diabetic rats

“…The AAR of rat hearts was homogenized in 0.9 % NaCl (1:10, wt/vol). The tissue homogenate was centrifuged at 12,000 g for 10 min at 4 °C, and the supernatant was collected to determine myocardial eNOS activity using a spectrophotometrical assay kit (Nanjing Jiancheng Bioengineering) as previously reported [ 21 , 24 ].…”

“…Acetylated eNOS antibody was not commercially available up to now. The expression of eNOS acetylation was determined by co-immunoprecipitation assay as described in our previous study [ 24 ]. eNOS (1:1000 crosslinked to magnetic beads (Dynal, Invitrogen) for extraction) was immunoprecipitated from 40 μg of myocardial tissue lysate, and the primary antibody for acetyl-lysine (Cell signaling) was employed to detect the association of the acetyl-lysine with eNOS by using immunoblotting.…”

Caloric Restriction and Its Effect on Blood Pressure, Heart Rate Variability and Arterial Stiffness and Dilatation: A Review of the Evidence

“…An activator of SIRT1 normalised SIRT1 expression in aged mice and restored endothelium-dependent vasodilatation by enhancing cyclooxygenase (COX)-2 signalling and reducing inflammation and oxidative stress in the elderly animals [ 99 ]. Another animal study showed that CR-improved endothelial function was associated with restored eNOS phosphorylation and SIRT1 expression, but reduced eNOS acetylation [ 100 ]. In eNOS-deficient mice, CR failed to exert an antihypertensive effect, as evidenced by elevated BP and absence of SIRT1 activity [ 101 ].…”