Acute hemodynamic changes in cardiovascular disease rat models exposed to Ractopamine.
Date Issued
2014
Date
2014
Author(s)
Tsai, Pei-Jing
Abstract
Ractopamine hydrochloride (RAC) is authorized for use in feed destined for specific poultry and livestock in some countries to improve feed efficiency, weight gain and carcass leanness, increase in muscle mass and decrease in body fat. Although RAC is not for use in humans, people may be exposed to it through the consumption of meat and internal organs containing RAC residues. The dose-dependent effects of RAC in specific organs and systems were studied in a limited number of studies in healthy animals and human volunteer subjects. And the recently-adopted maximum residue limits (MRLs) for RAC are based on the results of above studies. Pharmacologically, RAC is a β-adrenergic agonist, as it could activate both β1- and β2-adrenergic receptors. Although compared to other β-adrenergic agonists, RAC is lower in toxicity and can be rapidly metabolized; its CV toxicity for the consumers is still a concern. Since patients with underlying cardiovascular diseases are often more susceptible to agents with CV toxicity, more studies should be conducted to determine whether or no more stringent MRLs of residual RAC in meats should be recommended. Therefore, we aim to investigate the acute hemodynamic effects of RAC in rats between 12-13 weeks of age with underlying cardiovascular disease (CVD).
Forty-eight male Wistar Kyoto (WKY) rats were randomizedly divided into atherosclerotic (AW) group and control group. Additional twenty-four spontaneously hypertensive rats (SHRs) were selected as an animal model of primary hypertension. Early AS lesions were induced by chronic administration of N omega-nitro-L-arginine methyl ester in drinking water and feeding a high-cholesterol (1%) diet. Dose-response relationships between RAC exposure and acute hemodynamic changes of rats were investigated following oral administration at different dosage levels of 0, 3, 9 and 27 mg/kg bw of RAC by gastric intubation. Hemodynamic parameters in rats with different disease model and dosage were measured using a high-fidelity pressure-volume catheter positioned in the chamber of left ventricle, and two high-fidelity pressure transducers at the left carotid and femoral arteries of each rat. Continuous recordings were collected beginning 5 minutes (min) before exposure until 60 min after exposure. The data were analyzed on a beat-to-beat basis and reported as 2- or 5- min periods.
Our results revealed that three rat groups showed different dose-response relationship and time course with respect to RAC exposure. As expected, these findings are more prominent in rats with underlying CVD. Increasing heart rate (HR), increasing cardiac output (CO) and decreasing peripheral vascular resistance (TPR) were observed in all highest-dose subgroups. A significant decrease of blood pressure was observed in SHRs exposed to the highest-dose of RAC. Relative to this finding, a significant elevation of SBP was observed in AW rats exposed to 9 mg/kg bw of RAC. Based on our findings, more studied should be conducted to confirm the cardiovascular toxicity of RAC in susceptible populations and make reference to safety limits of residual RAC for meats.
Subjects
萊克多巴胺
心血管毒性
動脈硬化
高血壓
血行動力學
Type
thesis
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