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Pioglitazone opposes neurogenic vascular dysfunction associated with chronic hyperinsulinaemia
S Takatori1, Y Zamami, N Yabumae
1Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
British Journal of Pharmacology
|February 5, 2008
Summary
Pioglitazone treatment in fructose-fed rats improved vascular dysfunction linked to hyperinsulinemia. It normalized adrenergic nerve-mediated vasoconstriction and calcitonin gene-related peptide nerve-mediated vasodilation.
Area of Science:
- Cardiovascular Pharmacology
- Endocrinology
- Vascular Physiology
Background:
- Chronic hyperinsulinemia, induced by high fructose intake, alters vascular function.
- It enhances adrenergic nerve-mediated vasoconstriction.
- It suppresses calcitonin gene-related peptide (CGRP)-mediated vasodilation.
Purpose of the Study:
- To investigate the effects of pioglitazone on vascular responses in fructose-fed rats.
- To assess pioglitazone's impact on adrenergic and CGRPergic nerve function in hyperinsulinemia.
- To evaluate pioglitazone's efficacy in correcting vascular dysregulation.
Main Methods:
- Utilized pithed rats, with and without fructose-induced hyperinsulinemia (FDR).
- Administered pioglitazone orally to FDR for two weeks.
- Assessed vascular responses to spinal cord stimulation (SCS), noradrenaline, angiotensin II, and CGRP injections.
Main Results:
- Fructose-fed rats exhibited augmented vasoconstriction and impaired vasodilation.
- Pioglitazone treatment significantly reduced plasma insulin, triglycerides, and glucose levels.
- Pioglitazone diminished exaggerated vasoconstrictor responses and improved vasodilator responses in FDR.
Conclusions:
- Pioglitazone effectively improves insulin resistance in fructose-fed rats.
- Pioglitazone ameliorates vascular control dysfunctions mediated by adrenergic and CGRPergic nerves.
- The drug offers a potential therapeutic strategy for vascular complications associated with hyperinsulinemia.
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