Fenugreek (Trigonella Foenum-Graecum) Seed Flour and Diosgenin Preserve Endothelium-Dependent Arterial Relaxation in a Rat Model of Early-Stage Metabolic Syndrome

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FSCPX, a chemical widely used as an irreversible A1 adenosine receptor antagonist, modifies the effect of NBTI, a nucleoside transport inhibitor, by reducing the interstitial adenosine level in the guinea pig atrium

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Protective Effect of Prunus Cerasus (Sour Cherry) Seed Extract on the Recovery of Ischemia/Reperfusion-Induced Retinal Damage in Zucker Diabetic Fatty Rat

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Negative Inotropic Effect of BGP-15 on the Human Right Atrial Myocardium

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Nicotinic-acid derivative BGP-15 improves diastolic function in a rabbit model of atherosclerotic cardiomyopathy

Background and purpose: Small molecule BGP-15 has been reported to alleviate signs of heart failure and improve muscle function in murine models. Here, we investigated the acute and chronic effects of BGP-15 in a rabbit model of atherosclerotic cardiomyopathy. Experimental approach: Rabbits were maintained on standard chow (Control) or atherogenic diet (HC) for 16 weeks. BGP-15 was administered intravenously (once) or orally (for 16 weeks), to assess acute and chronic effects. Cardiac function was evaluated by echocardiography, endothelium-dependent vasorelaxation was assessed, and key molecules of the protein kinase G (PKG) axis were examined by ELISA and Western blot. Passive force generation was investigated in skinned cardiomyocytes. Key results: Both acute and chronic BGP-15 treatment improved the diastolic performance of the diseased heart, however, vasorelaxation and serum lipid markers were unaffected. Myocardial cGMP levels were elevated in the BGP-15-treated group, along with preserved PKG activity and increased phospholamban Ser16-phosphorylation. PDE5 expression decreased in the BGP-15-treated group, and the substance inhibited PDE1 enzyme. Cardiomyocyte passive tension reduced in BGP-15-treated rabbits, the ratio of titin N2BA/N2B isoforms increased, and PKG-dependent N2B-titin phosphorylation elevated in the BGP-15-treated group. Conclusions and implications: Here we report that BGP-15-treatment improves diastolic function, reduces cardiomyocyte stiffness, and restores titin compliance in a rabbit model of atherosclerotic cardiomyopathy by increasing the activity of the cGMP-PKG axis. As BGP-15 is proven to be safe, it may have clinical value in the treatment of diastolic dysfunction