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Pioglitazone, a PPARgamma agonist, restores endothelial function in aorta of streptozotocin-induced diabetic rats.
Cardiovasc Res. 2005 Apr 01; 66(1):150-61.CR

Abstract

OBJECTIVE

To study the effect of pioglitazone (a PPAR gamma agonist) treatment on blood pressure, endothelial function, and oxidative stress in streptozotocin (STZ)-induced diabetic rats.

METHODS

Sprague-Dawley rats were randomized into control (n=32) and STZ-diabetic (n=32) groups. Rats were further randomized to receive pioglitazone (10 mg/kg) or placebo for 4 weeks, and the following protocols were carried out. Blood pressure, blood glucose level, and body weight were measured. Thoracic aorta was isolated and the dose-response curve of phenylephrine (PE) in the presence or absence of Nomega-nitro-L-arginine-methyl ester (L-NAME) was recorded. The dose-response curve of acetylcholine (Ach) in the presence or absence of indomethacin, L-NAME, and methylene blue was recorded. Tone-related basal nitric oxide release experiments were carried out. Lipid peroxidation, superoxide dismutase, catalase, and reduced glutathione were estimated in liver, kidney, and aorta. Aortic nitrite levels were also measured. Further, in vitro effects of PE and Ach in the presence of pioglitazone (0.1 M-10 mM) were measured in aortic rings of nondiabetic and STZ-diabetic rats. Pioglitazone-induced relaxations were recorded in PE-contracted rings (with intact and denuded endothelium) in the presence of L-NAME and in KCl-contracted rings.

RESULTS

Pioglitazone treatment reduced blood pressure without having any significant effect on blood glucose level and body weight of STZ-diabetic rats. Enhanced PE-induced contraction and impaired Ach-induced relaxations in STZ-diabetic rats were restored to normal by pioglitazone treatment. The presence of L-NAME but not indomethacin blocked Ach-induced relaxation in pioglitazone-treated STZ-diabetic rats. Basal nitric oxide release was significantly higher in pioglitazone-treated STZ-diabetic rats. Oxidative stress was significantly higher in STZ-diabetic rats and pioglitazone treatment significantly reduced it. High aortic nitrite levels of STZ-diabetic rats were significantly reduced by pioglitazone treatment. The presence of pioglitazone at higher concentrations (>10 muM), but not at lower concentrations, significantly changed the dose-response curve of PE or Ach. Pioglitazone relaxations at lower concentrations but not at higher concentrations were blocked by endothelium removal or by the presence of L-NAME.

CONCLUSION

Pioglitazone administration reduced oxidative stress, which prevented the breakdown of nitric oxide and increased nitric oxide levels, thereby restoring the endothelial function in aorta of STZ-diabetic rat. Hence, from the present study it can be concluded that pioglitazone administration in STZ-diabetic rats lowers blood pressure, protects against oxidative stress, 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 availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15769458

Citation

Majithiya, Jayesh B., et al. "Pioglitazone, a PPARgamma Agonist, Restores Endothelial Function in Aorta of Streptozotocin-induced Diabetic Rats." Cardiovascular Research, vol. 66, no. 1, 2005, pp. 150-61.
Majithiya JB, Paramar AN, Balaraman R. Pioglitazone, a PPARgamma agonist, restores endothelial function in aorta of streptozotocin-induced diabetic rats. Cardiovasc Res. 2005;66(1):150-61.
Majithiya, J. B., Paramar, A. N., & Balaraman, R. (2005). Pioglitazone, a PPARgamma agonist, restores endothelial function in aorta of streptozotocin-induced diabetic rats. Cardiovascular Research, 66(1), 150-61.
Majithiya JB, Paramar AN, Balaraman R. Pioglitazone, a PPARgamma Agonist, Restores Endothelial Function in Aorta of Streptozotocin-induced Diabetic Rats. Cardiovasc Res. 2005 Apr 1;66(1):150-61. PubMed PMID: 15769458.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pioglitazone, a PPARgamma agonist, restores endothelial function in aorta of streptozotocin-induced diabetic rats. AU - Majithiya,Jayesh B, AU - Paramar,Arvind N, AU - Balaraman,R, PY - 2004/07/19/received PY - 2004/12/23/revised PY - 2004/12/28/accepted PY - 2005/3/17/pubmed PY - 2005/8/6/medline PY - 2005/3/17/entrez SP - 150 EP - 61 JF - Cardiovascular research JO - Cardiovasc Res VL - 66 IS - 1 N2 - OBJECTIVE: To study the effect of pioglitazone (a PPAR gamma agonist) treatment on blood pressure, endothelial function, and oxidative stress in streptozotocin (STZ)-induced diabetic rats. METHODS: Sprague-Dawley rats were randomized into control (n=32) and STZ-diabetic (n=32) groups. Rats were further randomized to receive pioglitazone (10 mg/kg) or placebo for 4 weeks, and the following protocols were carried out. Blood pressure, blood glucose level, and body weight were measured. Thoracic aorta was isolated and the dose-response curve of phenylephrine (PE) in the presence or absence of Nomega-nitro-L-arginine-methyl ester (L-NAME) was recorded. The dose-response curve of acetylcholine (Ach) in the presence or absence of indomethacin, L-NAME, and methylene blue was recorded. Tone-related basal nitric oxide release experiments were carried out. Lipid peroxidation, superoxide dismutase, catalase, and reduced glutathione were estimated in liver, kidney, and aorta. Aortic nitrite levels were also measured. Further, in vitro effects of PE and Ach in the presence of pioglitazone (0.1 M-10 mM) were measured in aortic rings of nondiabetic and STZ-diabetic rats. Pioglitazone-induced relaxations were recorded in PE-contracted rings (with intact and denuded endothelium) in the presence of L-NAME and in KCl-contracted rings. RESULTS: Pioglitazone treatment reduced blood pressure without having any significant effect on blood glucose level and body weight of STZ-diabetic rats. Enhanced PE-induced contraction and impaired Ach-induced relaxations in STZ-diabetic rats were restored to normal by pioglitazone treatment. The presence of L-NAME but not indomethacin blocked Ach-induced relaxation in pioglitazone-treated STZ-diabetic rats. Basal nitric oxide release was significantly higher in pioglitazone-treated STZ-diabetic rats. Oxidative stress was significantly higher in STZ-diabetic rats and pioglitazone treatment significantly reduced it. High aortic nitrite levels of STZ-diabetic rats were significantly reduced by pioglitazone treatment. The presence of pioglitazone at higher concentrations (>10 muM), but not at lower concentrations, significantly changed the dose-response curve of PE or Ach. Pioglitazone relaxations at lower concentrations but not at higher concentrations were blocked by endothelium removal or by the presence of L-NAME. CONCLUSION: Pioglitazone administration reduced oxidative stress, which prevented the breakdown of nitric oxide and increased nitric oxide levels, thereby restoring the endothelial function in aorta of STZ-diabetic rat. Hence, from the present study it can be concluded that pioglitazone administration in STZ-diabetic rats lowers blood pressure, protects against oxidative stress, and restores endothelial function. SN - 0008-6363 UR - https://www.unboundmedicine.com/medline/citation/15769458/Pioglitazone_a_PPARgamma_agonist_restores_endothelial_function_in_aorta_of_streptozotocin_induced_diabetic_rats_ L2 - https://academic.oup.com/cardiovascres/article-lookup/doi/10.1016/j.cardiores.2004.12.025 DB - PRIME DP - Unbound Medicine ER -