Troglitazone and metformin, but not glibenclamide, decrease blood pressure in Otsuka Long Evans Tokushima Fatty rats.

Area of Science:

• Endocrinology
• Pharmacology
• Cardiovascular Research

Background:

• Non-insulin-dependent diabetes mellitus (NIDDM) is often associated with insulin resistance and hypertension.
• Hypoglycemic agents are used to manage blood glucose levels in NIDDM.
• The cardiovascular effects of these agents, particularly in the context of insulin resistance, require further investigation.

Purpose of the Study:

• To evaluate the hypotensive effects of sulfonylureas, biguanides, and insulin sensitizers in an animal model of NIDDM with insulin resistance.
• To compare the effects of glibenclamide, metformin, and troglitazone on blood pressure and related metabolic parameters.

Main Methods:

• Male Otsuka Long Evans Tokushima Fatty (OLETF) rats were treated with glibenclamide, metformin, or troglitazone for 26 weeks.
• Fasting plasma glucose, insulin response to glucose loading, serum triglyceride levels, and systolic blood pressure were measured.
• Plasma membrane GLUT4 protein content, plasma norepinephrine, and epinephrine were also assessed.

Main Results:

• Troglitazone significantly decreased fasting plasma glucose and insulin AUC during glucose loading.
• Metformin and troglitazone significantly reduced systolic blood pressure after 29 weeks of age, unlike glibenclamide.
• Troglitazone treatment led to lower serum triglyceride levels compared to glibenclamide.
• GLUT4 protein content increased with glibenclamide and tended to increase with metformin.

Conclusions:

• Metformin and troglitazone demonstrate significant blood pressure-lowering effects in an insulin-resistant rat model.
• Glibenclamide did not exhibit hypotensive effects and was associated with increased systolic blood pressure.
• These findings support the beneficial role of insulin-sensitizing hypoglycemic agents in managing blood pressure in NIDDM.