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

• Published in: Blood pressure Vol. 10; no. 3; pp. 164 - 169
• Main Authors: Alberto Aguilar-Salinas, Carlos, Adriana Arellano, Sagrario, Villanueva-Sanchez, Octavio, Magos, Gil A., Guillén-Pineda, Luz E., Rodriguez, Rodolfo, Gómez-Pérez, Francisco J.
• Format: Journal Article
• Language: English
• Published: Stockholm Informa UK Ltd 2001; Taylor & Francis
• Subjects: Animals; Antihypertensive Agents - administration & dosage; Antihypertensive Agents - pharmacology; Associated diseases and complications; Biological and medical sciences; Blood Glucose - drug effects; Blood Pressure - drug effects; Blood Pressure Fosinopril Insulin Resistance Omapatrilat Zucker Rats; Diabetes. Impaired glucose tolerance; Double-Blind Method; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Fosinopril - administration & dosage; Fosinopril - pharmacology; Glucose Tolerance Test; Insulin - blood; Insulin Resistance; Male; Medical sciences; Models, Animal; Obesity; Pyridines - administration & dosage; Pyridines - pharmacology; Rats; Rats, Zucker; Thiazepines - administration & dosage; Thiazepines - pharmacology; Triglycerides - blood; Endocrinopathy; Animal model; Systolic pressure; Rat; Glucose; Omapatrilat; Arterial pressure; Nutritional status; Obesity; Fasting; Diabetes mellitus; Rodentia; Nutrition disorder; Oral administration; Glucose tolerance test; Triglyceride; Insulin; Target tissue resistance; Vertebrata; Chemotherapy; Mammalia; Treatment; Animal; Antihypertensive agent; Fosinopril; ACE inhibitor
• ISSN: 0803-7051; 1651-1999
• DOI: 10.1080/080370501753182389

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 &#45 9 vs 125 &#45 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.