Vasonatrin Peptide VNP

Vasonatrin peptide, a synthetic natriuretic peptide, attenuates myocardial injury and oxidative stress in isoprenaline-induced cardiomyocyte hypertrophy

Isoprenaline-induced cardiac hypertrophy can deteriorate to heart failure, which is a leading cause of mortality. Endogenous vasonatrin peptide (VNP) has been reported to be cardioprotective against myocardial ischemia/reperfusion injury in diabetic rats. However, little is known about the effect of exogenous VNP on cardiac hypertrophy. We further explored whether VNP attenuated isoprenaline-induced cardiomyocyte hypertrophy by examining the levels and activities of cGMP and PKG. In this study, we found that VNP significantly attenuated isoprenaline-induced myocardial hypertrophy and cardiac fibroblast activation in vivo. Moreover, VNP effectively halted the activation of apoptosis and oxidative stress in the isoprenaline-treated myocardium. VNP promoted superoxide dismutase (SOD) activity. Further study revealed that the protective effects of VNP might be mediated by the activity of the cGMP-PKG signaling pathway in vivo or in vitro, while the use of agonists and antagonists confirmed these results. Therefore, we demonstrated that the antiapoptosis and antioxidative stress effects of VNP depends on elevated cGMP-PKG signaling activity both in vivo and in vitro. These results suggest that VNP may be used in the treatment of myocardial hypertrophy.

The Effects of Vasonatrin Peptide on Fat Graft Viability: An Experimental Study

Vasonatrin peptide (VNP) is a synthetic peptide that possesses vasodilatory, natriuretic, and anti-inflammatory properties. The authors aimed to analyze the effects of VNP on fat graft survival. Twenty Sprague-Dawley rats are randomly divided into two groups of 10. Fat grafts are harvested from the right inguinal region. After preparation, fat grafts are placed to the interscapular region. The first group of rats were administered VNP after their fat injection, while the second group received tail-vein injections of an equal volume of sterile saline following their fat injection. Experiment and control groups are evaluated according to their level of degeneration of adipocytes, fat necrosis, vacuolization, cyst formation in adipocytes, fibrosis of the fat tissue, capillary density, and CD31 immunohistochemical staining. Degeneration, vacuolization, and cyst formation in adipocytes were lower in the experiment group. Increased capillary density in the experiment group was demonstrated by CD31 antibody staining and by counting capillary density under a microscope. The average percentage of change in weight of the fat grafts in the experiment group was lower than that in the control group. The results indicate that VNP has some beneficial effects on fat graft survival by multiple independent mechanisms that influence both local and systemic homeostasis.

Vasonatrin peptide attenuates myocardial ischemia-reperfusion injury in diabetic rats and underlying mechanisms

Diabetes mellitus increases morbidity/mortality of ischemic heart disease. Although atrial natriuretic peptide and C-type natriuretic peptide reduce the myocardial ischemia-reperfusion damage in nondiabetic rats, whether vasonatrin peptide (VNP), the artificial synthetic chimera of atrial natriuretic peptide and C-type natriuretic peptide, confers cardioprotective effects against ischemia-reperfusion injury, especially in diabetic patients, is still unclear. This study was designed to investigate the effects of VNP on ischemia-reperfusion injury in diabetic rats and to further elucidate its mechanisms. The high-fat diet-fed streptozotocin-induced diabetic Sprague-Dawley rats were subjected to ischemia-reperfusion operation. VNP treatment (100 μg/kg iv, 10 min before reperfusion) significantly improved the instantaneous first derivation of left ventricle pressure (±LV dP/dtmax) and LV systolic pressure and reduced LV end-diastolic pressure, apoptosis index, caspase-3 activity, plasma creatine kinase (CK), and lactate dehydrogenase (LDH) activities. Moreover, VNP inhibited endoplasmic reticulum (ER) stress by suppressing glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP). These effects were mimicked by 8-bromine-cyclic guanosinemonophosphate (8-Br-cGMP), a cGMP analog, whereas they were inhibited by KT-5823, the selective inhibitor of PKG. In addition, pretreatment with tauroursodeoxycholic acid (TUDCA), a specific inhibitor of ER stress, could not further promote the VNP's cardioprotective effect in diabetic rats. In vitro H9c2 cardiomyocytes were subjected to hypoxia/reoxygenation and incubated with or without VNP (10(-8) mol/l). Gene knockdown of PKG1α with siRNA blunted VNP inhibition of ER stress and apoptosis, while overexpression of PKG1α resulted in significant decreased ER stress and apoptosis. VNP protects the diabetic heart against ischemia-reperfusion injury by inhibiting ER stress via the cGMP-PKG signaling pathway. These results suggest that VNP may have potential therapeutic value for the diabetic patients with ischemic heart disease.

Vasonatrin peptide stimulates both of the natriuretic peptide receptors, NPRA and NPRB

Vasonatrin peptide (VNP) is an active cardiovascular factor and a novel synthetic natriuretic peptide with unknown natriuretic peptide receptor (NPR) binding properties. We set out to design binding models of NPRA/VNP and NPRB/VNP, and then assessed their recognition and binding affinities using molecular dynamics. Molecular dynamics analysis indicated decreases in the values of Van der Waals, electrostatic energy and potential energy of NPRB/VNP compared to NPRA/VNP. There was a 25% increase in H-bond formation between VNP and NPRB. The cGMP stimulated by VNP in NPRB-transfected HEK-293 cells was 11-fold higher than that of NPRA. We therefore demonstrated that VNP binds with both NPRA and NPRB, but with a preference for NPRB.

The effects of vasonatrin peptide on random pattern skin flap survival

Background: A lot of methods have been intensively investigated to improve random skin flap survival. Decreasing inflammation and alleviating tissue injury have been reported to be effective in improving survival ratio. Vasonatrin peptide (VNP) is a chimera of atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP). The current study demonstrates that VNP possesses the venodilating actions of CNP, the natriuretic actions of ANP, and the unique arterial vasodilating actions not associated with either ANP or CNP. However, its effects on skin flap survival have not been previously reported.
Methods: Sprague-Dawley rats, weighing 220 to 260 g, were randomly divided into 2 groups, namely, the VNP-treated group and the control group. Rectangular random dorsal skin flaps measuring 3 × 9 cm including the panniculus carnosus were elevated, then the flaps were sutured into their original places. In the VNP group, 0.1 mg/kg of VNP was administered intravenously (IV) after surgery and then daily for 3 days. In the control group, 1 mL/kg of saline was administered IV after surgery and then daily for 3 days. To observe the effects of VNP, blood perfusion, histopathological examination, the inflammatory mediators (tumor necrosis factor α, interleukin 1β, and interferon γ), and biochemical analysis (malondialdehyde, glutathione, and myeloperoxidase) were detected and the flap viability was evaluated 7 days after surgery by measuring necrotic flap area and total flap area.
Results: The viability measurements showed the percentage of flap survival was increased in the VNP-treated group (76.53% ± 6.36%) as compared with the control group (61.12% ± 4.92%) (P < 0.05), and the histological and biochemical assays corroborated the data. The blood perfusion of flaps in the VNP-treated group was higher than the control group (P < 0.05). The inflammatory mediators (tumor necrosis factor α, interleukin 1β, and interferon γ) were significantly lower in the VNP-treated group than the control group (P < 0.05).
Conclusions: This study found that VNP, which could elevate the tissue blood perfusion and mitigate the tissue damage and inflammatory reaction, is associated with a higher percentage of survival random pattern skin flap area.