Effects of omapatrilat on blood pressure and insulin sensitivity in an animal model of insulin resistance.
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.


METHODS
Double blind, parallel, prospective trial.


METHODS
Forty-two male obese Zucker (falfa) 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 micromol/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.
Aguilar-Salinas
C A
CA
Departamento de Endocrinologia y Metabolismo, Unidad de Investigación Experimental, Instituto Nacional de la Nutrición, México City, México. caas@aztlan.innsz.mx
Arellano
S A
SA
Villanueva-Sanchez
O
O
Magos
G A
GA
Guillén-Pineda
L E
LE
Rodriguez
R
R
Gómez-Pérez
F J
FJ
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D004311:Double-Blind Method; D017328:Fosinopril / Q000008:administration & dosage / Q000494:pharmacology; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D023421:Models, Animal; D009765:Obesity; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011924:Rats, Zucker; D013841:Thiazepines / Q000008:administration & dosage / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
D000959:Antihypertensive Agents; D001786:Blood Glucose; D007328:Insulin; D011725:Pyridines; D013841:Thiazepines; D014280:Triglycerides; C106266:omapatrilat; D017328:Fosinopril