Oral administration of HPβCD/Ang-(1-7) reduced the infarcted area by 50% and attenuated heart function impairment and cardiac remodeling in infarcted and isoproterenol-treated rats.
Does oral HPβCD/Ang-(1-7) improve cardiac function and reduce infarct size in infarcted and isoproterenol-treated rats?
An oral formulation of Ang-(1-7) in HPβCD produces cardioprotective effects, reducing infarct size and attenuating cardiac remodeling in rat models of myocardial injury.
In this study we evaluated the cardiac effects of a pharmaceutical formulation developed by including angiotensin (Ang)-(1-7) in hydroxypropyl β-cyclodextrin (HPβCD), in normal, infarcted, and isoproterenol-treated rats. Myocardial infarction was produced by left coronary artery occlusion. Isoproterenol (2 mg/kg, IP) was administered daily for 7 days. Oral administration of HPβCD/Ang-(1-7) started immediately before infarction or associated with the first dose of isoproterenol. After 7 days of treatment, the rats were euthanized, and the Langendorff technique was used to analyze cardiac function. In addition, heart function was chronically (15, 30, 50 days) analyzed by echocardiography. Cardiac sections were stained with hematoxylin/eosin and Masson trichrome to evaluate cardiac hypertrophy and damage, respectively. Pharmacokinetic studies showed that oral HPβCD/Ang-(1-7) administration significantly increased Ang-(1-7) on plasma whereas with the free peptide it was without effect. Oral administration of HPβCD/Ang-(1-7) (30 μg/kg) significantly reduced the deleterious effects induced by myocardial infarction on systolic and diastolic tension, ±dT/dt, perfusion pressure, and heart rate. Strikingly, a 50% reduction of the infarcted area was observed in HPβCD/Ang-(1-7)-treated rats. Furthermore, HPβCD/Ang-(1-7) attenuated the heart function impairment and cardiac remodeling induced by isoproterenol. In infarcted rats chronically treated with HPβCD/Ang-(1-7), the reduction of ejection fraction and fractional shorting and the increase in systolic and diastolic left ventricular volumes observed in infarcted rats were attenuated. Altogether, these findings further confirm the cardioprotective effects of Ang-(1-7). More importantly, our data indicate that the HPβCD/Ang-(1-7) is a feasible formulation for oral administration of Ang-(1-7), which can be used as a cardioprotective drug.
Marques et al. (Tue,) conducted a other in Myocardial infarction and isoproterenol-induced cardiac damage. Oral HPβCD/Ang-(1-7) vs. Untreated infarcted/isoproterenol-treated rats was evaluated on Cardiac function, infarcted area, and cardiac remodeling. Oral administration of HPβCD/Ang-(1-7) reduced the infarcted area by 50% and attenuated heart function impairment and cardiac remodeling in infarcted and isoproterenol-treated rats.