Metformin reverses the effect of high glucose on mesenteric artery relaxation in normal rats

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Elevated glucose produces alterations in the cardiovascular system, which affect the health of subjects with these increases, which affect systems such as the gastrointestinal, since the mesenteric arteries play an important role for the proper development of the individual. These diseases are related and cause great morbidity and mortality worldwide. Metformin is a biguanide used to control blood glucose levels. This study assessed the effect of metformin on arterial tension and endothelial function on rat normal mesenteric arteries. Arteries incubated in glucose (30 mM) demonstrated a profoundly impaired endothelium-dependent relaxation to acetylcholine. The treatment with metformin (1 mM) produced the change in the vascular activity, like the control group. These results indicated that the action of metformin in the vascular activity is recovered to normal condition, which is important in patients with diabetes mellitus type 2, already the cardiovascular alterations were presents in these patients. Glucose modified the effect of Nitric oxide synthase and CYTP450, decreasing the production of Nitric Oxide and hyperpolarizing factor, in arteries relaxed with acetylcholine, where metformin reversed to normal conditions. On the other hand, the used of metformin plus indomethacin produced inhibition on metformin, effects inducing a mayor inhibition on the vascular relaxation to acetylcholine. Also, metformin presented a minimum effect on K+ channels, when are inactivated with TEA, recovering of manner partial the action of this channel, increased relaxation effect by acetylcholine. Metformin effect is not due to osmotic control or oxidative stress. An important effect is the use of analgesics such as indomethacin, which produces dysfunction of the vascular endothelium, generating the presence of diseases due to the state of hypertension obtained in the mesenteric arteries, affecting the proper functioning of the gastrointestinal system, decreasing the uptake of nutrients and presenting various diseases.