Effects of Omapatrilat on Blood Pressure and Insulin Sensitivity in an Animal Model of Insulin Resistance

Abstract

Objective: To assess the effects of omapatrilat, fosinopril and placebo on blood pressure, plasma insulin, glucose and triglycerides concentrations in Zucker rats, a model for insulin resistance. Design: Double blind, parallel, prospective trial. Methods: Forty-two male obese Zucker ( fa / fa ) rats (aged 13-18 week) initially weighing 400-600 g were used for the experiments. Omapatrilat ( n = 14), placebo ( n = 14) or fosinopril ( n = 14) were administrated once daily at 10 µmol/kg oral for 15 days. At baseline and at the end of the study, a tail-cuff blood pressure measurement was performed; an oral glucose tolerance test was done at the end of the study. Results: Omapatrilat and fosinopril resulted in significant lower systolic blood pressure compared to the placebo group ( p < 0.001). This parameter was significantly lower in the omapatrilat group compared with fosinopril-treated rats (116 - 9 vs 125 - 4 mmHg, p < 0.05). After an overnight fast, there was no difference in the fasting glucose concentrations among treatment groups. The basal and post-glucose challenge insulin concentrations were lower in the omapatrilat group compared to the placebo group. No difference was observed in the fasting triglycerides concentrations between the treatment groups. Conclusions: Compared to placebo and fosinopril treatment, omapatrilat results in lower arterial blood pressure in an animal model of insulin resistance. The results suggest that omapatrilat may have a positive effect on insulin sensitivity.