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Metformin reduces blood pressure and restores endothelial function in aorta of streptozotocin-induced diabetic rats.
Life Sci. 2006 Apr 25; 78(22):2615-24.LS

Abstract

Effect of metformin treatment on blood pressure, endothelial function and oxidative stress in streptozotocin (STZ)-induced diabetes in rats was studied. In vitro effect of metformin on vascular reactivity to various agonist in the presence of metformin in untreated nondiabetic and STZ-diabetic rats were also studied. Sprague-Dawley rats were randomized into nondiabetic and STZ-diabetic groups. Rats were further randomized to receive metformin (150 mg/kg) or vehicle for 4 weeks. Metformin treatment reduced blood pressure without having any significant effect on blood glucose level in STZ-diabetic rats. Enhanced phenylephrine (PE)-induced contraction and impaired acetylcholine (Ach)-induced relaxation in STZ-diabetic rats were restored to normal by metformin treatment. Enhanced Ach-induced relaxation in metformin-treated STZ-diabetic rats was blocked due to pretreatment with 100 microM of Nomega-nitro-L-arginine-methyl ester (L-NAME) or 10 microM of methylene blue but not 10 microM of indomethacin. Metformin treatment significantly increased antioxidant enzymes and reduced lipid peroxidation in STZ-diabetic rats. In vitro studies in aortic rings of untreated nondiabetic and STZ-diabetic rats showed that the presence of higher concentration of metformin (1 mM and 10 mM) significantly reduced PE-induced contraction and increased Ach-induced relaxation. Metformin per se relaxed precontracted aortic rings of untreated nondiabetic and STZ-diabetic rats in a dose-dependent manner. Pretreatment with L-NAME or removal of endothelium blocked metformin-induced relaxation at lower concentration (up to 30 microM) but not at higher concentration (above 30 microM). Metformin-induced relaxation was blocked in the presence of 1 mM of 4-aminopyridine, or 1 mM of tetraethylammonium but not in the presence of 100 microM of barium ion or 10 microM of glybenclamide. The restored endothelial function along with direct effect of metformin on aortic rings and reduced oxidative stress contributes to reduced blood pressure in STZ-diabetic rats. From the present study, it can be concluded that metformin administration to STZ-diabetic rats lowers blood pressure, and restores endothelial function.

Authors+Show Affiliations

Pharmacy Department, Faculty of Technology and Engineering, M. S. University of Baroda, Kalabhavan, Baroda-390001, Gujarat, India. jayeshbm@yahoo.comNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16318863

Citation

Majithiya, Jayesh B., and R Balaraman. "Metformin Reduces Blood Pressure and Restores Endothelial Function in Aorta of Streptozotocin-induced Diabetic Rats." Life Sciences, vol. 78, no. 22, 2006, pp. 2615-24.
Majithiya JB, Balaraman R. Metformin reduces blood pressure and restores endothelial function in aorta of streptozotocin-induced diabetic rats. Life Sci. 2006;78(22):2615-24.
Majithiya, J. B., & Balaraman, R. (2006). Metformin reduces blood pressure and restores endothelial function in aorta of streptozotocin-induced diabetic rats. Life Sciences, 78(22), 2615-24.
Majithiya JB, Balaraman R. Metformin Reduces Blood Pressure and Restores Endothelial Function in Aorta of Streptozotocin-induced Diabetic Rats. Life Sci. 2006 Apr 25;78(22):2615-24. PubMed PMID: 16318863.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Metformin reduces blood pressure and restores endothelial function in aorta of streptozotocin-induced diabetic rats. AU - Majithiya,Jayesh B, AU - Balaraman,R, Y1 - 2005/11/28/ PY - 2005/07/21/received PY - 2005/10/11/accepted PY - 2005/12/2/pubmed PY - 2006/5/19/medline PY - 2005/12/2/entrez SP - 2615 EP - 24 JF - Life sciences JO - Life Sci VL - 78 IS - 22 N2 - Effect of metformin treatment on blood pressure, endothelial function and oxidative stress in streptozotocin (STZ)-induced diabetes in rats was studied. In vitro effect of metformin on vascular reactivity to various agonist in the presence of metformin in untreated nondiabetic and STZ-diabetic rats were also studied. Sprague-Dawley rats were randomized into nondiabetic and STZ-diabetic groups. Rats were further randomized to receive metformin (150 mg/kg) or vehicle for 4 weeks. Metformin treatment reduced blood pressure without having any significant effect on blood glucose level in STZ-diabetic rats. Enhanced phenylephrine (PE)-induced contraction and impaired acetylcholine (Ach)-induced relaxation in STZ-diabetic rats were restored to normal by metformin treatment. Enhanced Ach-induced relaxation in metformin-treated STZ-diabetic rats was blocked due to pretreatment with 100 microM of Nomega-nitro-L-arginine-methyl ester (L-NAME) or 10 microM of methylene blue but not 10 microM of indomethacin. Metformin treatment significantly increased antioxidant enzymes and reduced lipid peroxidation in STZ-diabetic rats. In vitro studies in aortic rings of untreated nondiabetic and STZ-diabetic rats showed that the presence of higher concentration of metformin (1 mM and 10 mM) significantly reduced PE-induced contraction and increased Ach-induced relaxation. Metformin per se relaxed precontracted aortic rings of untreated nondiabetic and STZ-diabetic rats in a dose-dependent manner. Pretreatment with L-NAME or removal of endothelium blocked metformin-induced relaxation at lower concentration (up to 30 microM) but not at higher concentration (above 30 microM). Metformin-induced relaxation was blocked in the presence of 1 mM of 4-aminopyridine, or 1 mM of tetraethylammonium but not in the presence of 100 microM of barium ion or 10 microM of glybenclamide. The restored endothelial function along with direct effect of metformin on aortic rings and reduced oxidative stress contributes to reduced blood pressure in STZ-diabetic rats. From the present study, it can be concluded that metformin administration to STZ-diabetic rats lowers blood pressure, and restores endothelial function. SN - 0024-3205 UR - https://www.unboundmedicine.com/medline/citation/16318863/Metformin_reduces_blood_pressure_and_restores_endothelial_function_in_aorta_of_streptozotocin_induced_diabetic_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(05)01133-1 DB - PRIME DP - Unbound Medicine ER -