Monotherapy of experimental metabolic syndrome: II. Study of cardiovascular effects

Author:

Knezl Vladimír1,Sotníková Ružena1,Brnoliaková Zuzana1,Stankovičová Tatiana2,Bauer Viktor1,Bezek Štefan1

Affiliation:

1. Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Dúbravská 9, 841 04 Bratislava , Slovakia

2. Department of Pharmacology and Toxicology , Comenius University in Bratislava , Faculty of Pharmacy , Odbojárov 10, 832 32 Bratislava 3 , Slovakia

Abstract

Abstract Metabolic syndrome belongs to the most important risk factors of cardiovascular diseases. The aim of this study was to investigate changes in cardiovascular system induced by high cholesterol and high fat diet (HCHF) in HTG rats and their influence by a pyridoindole antioxidant – SMe1EC2 (S). The effects of S were compared with those of atorvastatin (A). Male HTG rats were fed HCHF (1% cholesterol + 7.5% lard) for 4 weeks. S and A were administered p.o., 50 mg/kg b.w. Following experimental groups were used: Wistar rats (W), hypertriglyceridemic rats (HTG), HTG rats fed HCHF (CHOL), HTG+S (S-HTG), CHOL+S (S-CHOL), and CHOL+A (A-CHOL). Values of blood pressure (BP) and selected ECG parameters were monitored in conscious animals, functions of the isolated heart and aorta were analyzed ex vivo. At the end of the experiment, systolic (sBP) and diastolic (dBP) blood pressure was increased in HTG and CHOL. S and A decreased BP in all treated groups. Accordingly with BP changes, the aortic endothelial function of CHOL was damaged. Both S and A administration ameliorated the endothelium-dependent relaxation to values of W. PQ and QTc intervals were prolonged in CHOL, while the treatment with S or A improved ECG findings. Prodysrhythmogenic threshold was decreased significantly in CHOL and both treatments returned it to the control values. In conclusion, HCHF increased BP, impaired endothelial relaxation of the aorta and potentiated susceptibility of myocardium to dysrhythmias. The effect of S on the changes induced by HCHF diet was more pronounced than that of A.

Publisher

Walter de Gruyter GmbH

Subject

Health, Toxicology and Mutagenesis,Pharmacology,Toxicology

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