Key result
Glyburide prevented or markedly attenuated minoxidil-induced cardiovascular lesions in dogs by blocking its profound hemodynamic effects without altering its pharmacokinetics.
Why the study?
Does blocking the pharmacologic effects of minoxidil with glyburide prevent minoxidil-induced cardiovascular toxicity in dogs?
Does blocking the pharmacologic effects of minoxidil with glyburide prevent minoxidil-induced cardiovascular toxicity in dogs?
The cardiovascular toxicity of minoxidil in dogs is driven by its profound hemodynamic effects rather than direct myocardial toxicity.
Supports hemodynamic mediation of minoxidil cardiotoxicity in dogs; leaves open human translation.
Minoxidil (MNX), like several other vasoactive drugs, causes cardiovascular toxicity in dogs by undetermined mechanisms. We studied the mechanism of cardiovascular toxicity of MNX [an adenosine triphosphate (ATP)-sensitive potassium channel opener] by blocking its pharmacologic effects with glyburide (an ATP-sensitive potassium channel blocker) in groups of 5 female beagle dogs treated orally for 2 days with 1.0 mg/kg/day of MNX alone or with glyburide given in 5 or 6 divided doses of 300 mg/kg at 2 hr before and after each dose of MNX and at 3-6-hr intervals thereafter. A third group of 5 dogs received glyburide alone in the same dosing regimen as in the combination group. Mean arterial pressure (MAP), heart rate (HR), the pharmacokinetics of MNX, and gross and microscopic changes in the heart were evaluated. Glyburide did not influence the pharmacokinetics of MNX but prevented or markedly attenuated the MNX-induced cardiovascular lesions (right atrial hemorrhagic lesions, subendocardial necrosis, or coronary arteritis) occurred in dogs whose MNX-induced hemodynamic effects were effectively blocked by glyburide. In conclusion, the cardiovascular toxicity of MNX in dogs is not caused by a direct toxic effect of MNX on the heart but apparently is related to the exaggerated pharmacologic/profound hemodynamic effects it elicits in the dog.
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Mesfin et al. (1995) studied Minoxidil-induced cardiovascular toxicity (n=15). Minoxidil with or without glyburide vs. Glyburide alone was evaluated on Cardiovascular lesions (right atrial hemorrhagic lesions, subendocardial necrosis, or coronary arteritis), hemodynamics, and pharmacokinetics. Glyburide prevented or markedly attenuated minoxidil-induced cardiovascular lesions in dogs by blocking its profound hemodynamic effects without altering its pharmacokinetics.
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