Glu298Asp variant of the endothelial nitric oxide synthase gene in patients with left ventricular dysfunction

Background: Growth hormone-releasing peptides (GHRP) have been reported to possess cardioprotective properties; nonetheless, their mechanisms of action are still not very clear. Objectives: Some studies have suggested that modulation of endothelial nitric oxide synthase (eNOS) and the upregulation of nitric oxide (NO) are cardioprotective. Therefore, the present study strived to test the hypothesis that a potent GHRP analog (hexarelin) could increase serum nitric oxide level and regulate myocardial eNOS to alleviate the development of heart failure. Methods: Myocardial infarction-induced heart failure in rats was established by permanent coronary artery ligation. The sham group, control group, and heart failure group all received normal saline (100 µg/kg; SC BID; 30days), while the rats in the hexarelin treatment group were treated with hexarelin (100 µg/kg, SC BID, 30 days). The rats were tested for myocardial apoptosis, oxidative stress, left ventricular function, various molecular analyses, as well as pathological and structural myocardial changes. Results: Hexarelin treatment improved contractile function and attenuated myocardial histopathological damages, oxidative stress, ﬁbrosis, as well as apoptosis. All these were accompanied by the upregulation of myocardial eNOS and an increase in serum NO concentration. Conclusion: As evidenced by the obtained results, the anti-cardiac failure capacity of hexarelinin in a rat model is mediated by an increase in serum nitric oxide level and the up-modulation of myocardial eNOS; therefore, they can be considered therapeutic targets against heart failure.

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Chronic hypoxia induces right heart failure in caveolin-1−/− mice

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01140.2011 ◽

2012 ◽

Vol 302 (12) ◽

pp. H2518-H2527 ◽

Cited By ~ 30

Author(s):

J. Agustin Cruz ◽

Eileen M. Bauer ◽

Andres I. Rodriguez ◽

Archana Gangopadhyay ◽

Nabil S. Zeineh ◽

...

Keyword(s):

Nitric Oxide ◽

Pulmonary Hypertension ◽

Nitric Oxide Synthase ◽

Endothelial Nitric Oxide Synthase ◽

Chronic Hypoxia ◽

Left Ventricular ◽

Caveolin 1 ◽

Oxide Synthase ◽

Endothelial Nitric Oxide ◽

Rv Function

Caveolin-1 (Cav-1)−/− mice develop mild pulmonary hypertension as they age. In this study, we sought to determine the effect of chronic hypoxia, an established model of pulmonary hypertension, on young Cav-1−/− mice with no measurable signs of pulmonary hypertension. Exposure of Cav-1−/− mice to chronic hypoxia resulted in an initial rise in right ventricular (RV) systolic pressure (RVSP) similar to wild-type (WT) mice. By three weeks RVSP decreased in the Cav-1−/− mice, whereas it was maintained in WT mice. The drop in RVSP in Cav-1−/− mice was accompanied by decreased cardiac output, increased RV hypertrophy, RV interstitial fibrosis, decreased RV sarco(endo)plasmic reticulum Ca2+-ATPase 2a mRNA and decreased RV function compared with WT mice. Importantly, minimal differences were noted in pulmonary vascular remodeling between WT and Cav-1−/− mice, and left ventricular function was normal in hypoxic Cav-1−/− mice. Mechanistically, increased endothelial nitric oxide synthase uncoupling and increased tyrosine nitration of protein kinase G were detected in the RV of Cav-1−/− mice. These hemodynamic, histological, and molecular changes were prevented in Cav-1−/− mice expressing an endothelial-specific Cav-1 transgene or by nitric oxide synthase inhibition. These data suggest that, in Cav-1−/− mice, increased oxidative/nitrosative stress due to endothelial nitric oxide synthase uncoupling modifies the response of the RV to pressure overload, accelerating the deterioration of RV function.

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Concentric left ventricular remodeling in endothelial nitric oxide synthase knockout mice by chronic pressure overload

Cardiovascular Research ◽

10.1016/j.cardiores.2005.01.021 ◽

2005 ◽

Vol 66 (3) ◽

pp. 444-453 ◽

Cited By ~ 80

Author(s):

H RUETTEN ◽

S DIMMELER ◽

D GEHRING ◽

C IHLING ◽

A ZEIHER

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Knockout Mice ◽

Endothelial Nitric Oxide Synthase ◽

Ventricular Remodeling ◽

Left Ventricular Remodeling ◽

Pressure Overload ◽

Left Ventricular ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

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Synthetic Pyridoindole and Rutin Affect Upregulation of Endothelial Nitric Oxide Synthase and Heart Function in Rats Fed a High-Fat-Fructose Diet

Physiological Research ◽

10.33549/physiolres.934670 ◽

2021 ◽

pp. 851-863

Author(s):

L. Salvaras ◽

T. Kovacic ◽

P. Janega ◽

B. Liptak ◽

M. Sasvariova ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Left Ventricle ◽

Endothelial Nitric Oxide Synthase ◽

Coronary Flow ◽

Left Ventricular ◽

Control Group ◽

High Fat ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

Metabolic syndrome (MetS) belongs to the serious health complications expanding in cardiovascular diseases, obesity, insulin resistance, and hyperglycemia. In this study, hypertriacylglycerolemic rats fed a high-fat-fructose diet (HFFD) were used as an experimental model of MetS to explore the effect of tested compounds. Effects of a new prospective pyridoindole derivative coded SMe1EC2 and the natural polyphenol rutin were tested. Endothelial nitric oxide synthase (NOS3) and nuclear factor kappa B (NF-κB) expression were assessed in the left ventricle immunohistochemically and left ventricle activity was monitored in isolated perfused rat hearts. NOS3 activity in the left ventricle decreased markedly as a result of a HFFD. NOS3 expression was upregulated by both substances. NF-κB expression was increased in the MetS group in comparison to control rats and the expression further increased in the SMe1EC2 treatment. This compound significantly improved the coronary flow in comparison to the control group during reperfusion of the heart followed after ischemia. Further, it tended to increase left ventricular systolic pressure, heart product, rate of maximal contraction and relaxation, and coronary flow during baseline assessment. Moreover, the compound SMe1EC2 decreased the sensitivity of hearts to electrically induced ventricular fibrillation. Contrary to this rutin decreased coronary flow in reperfusion. Present results suggest that despite upregulation of NOS3 by both substances tested, pyridoindole SMe1EC2 rather than rutin could be suitable in treatment strategies of cardiovascular disorders in MetS-like conditions.

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