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Azelnidipine prevents cardiac dysfunction in streptozotocin-diabetic rats by reducing intracellular calcium accumulation, oxidative stress and apoptosis.
Cardiovasc Diabetol. 2011 Nov 04; 10:97.CD

Abstract

BACKGROUND

Numerous evidences suggest that diabetic heart is characterized by compromised ventricular contraction and prolonged relaxation attributable to multiple causative factors including calcium accumulation, oxidative stress and apoptosis. Therapeutic interventions to prevent calcium accumulation and oxidative stress could be therefore helpful in improving the cardiac function under diabetic condition.

METHODS

This study was designed to examine the effect of long-acting calcium channel blocker (CCB), Azelnidipine (AZL) on contractile dysfunction, intracellular calcium (Ca2+) cycling proteins, stress-activated signaling molecules and apoptosis on cardiomyocytes in diabetes. Adult male Wistar rats were made diabetic by a single intraperitoneal (IP) injection of streptozotocin (STZ). Contractile functions were traced from live diabetic rats to isolated individual cardiomyocytes including peak shortening (PS), time-to-PS (TPS), time-to-relengthening (TR90), maximal velocity of shortening/relengthening (± dL/dt) and intracellular Ca2+ fluorescence.

RESULTS

Diabetic heart showed significantly depressed PS, ± dL/dt, prolonged TPS, TR90 and intracellular Ca2+ clearing and showed an elevated resting intracellular Ca2+. AZL itself exhibited little effect on myocyte mechanics but it significantly alleviated STZ-induced myocyte contractile dysfunction. Diabetes increased the levels of superoxide, enhanced expression of the cardiac damage markers like troponin I, p67phox NADPH oxidase subunit, restored the levels of the mitochondrial superoxide dismutase (Mn-SOD), calcium regulatory proteins RyR2 and SERCA2a, and suppressed the levels of the anti-apoptotic Bcl-2 protein. All of these STZ-induced alterations were reconciled by AZL treatment.

CONCLUSION

Collectively, the data suggest beneficial effect of AZL in diabetic cardiomyopathy via altering intracellular Ca2+ handling proteins and preventing apoptosis by its antioxidant property.

Authors+Show Affiliations

National Centre for Cell Science, NCCS Complex, Pune University Campus, Ganeshkhind Road, Pune-411007, Maharashtra, India.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

22054019

Citation

Kain, Vasundhara, et al. "Azelnidipine Prevents Cardiac Dysfunction in Streptozotocin-diabetic Rats By Reducing Intracellular Calcium Accumulation, Oxidative Stress and Apoptosis." Cardiovascular Diabetology, vol. 10, 2011, p. 97.
Kain V, Kumar S, Sitasawad SL. Azelnidipine prevents cardiac dysfunction in streptozotocin-diabetic rats by reducing intracellular calcium accumulation, oxidative stress and apoptosis. Cardiovasc Diabetol. 2011;10:97.
Kain, V., Kumar, S., & Sitasawad, S. L. (2011). Azelnidipine prevents cardiac dysfunction in streptozotocin-diabetic rats by reducing intracellular calcium accumulation, oxidative stress and apoptosis. Cardiovascular Diabetology, 10, 97. https://doi.org/10.1186/1475-2840-10-97
Kain V, Kumar S, Sitasawad SL. Azelnidipine Prevents Cardiac Dysfunction in Streptozotocin-diabetic Rats By Reducing Intracellular Calcium Accumulation, Oxidative Stress and Apoptosis. Cardiovasc Diabetol. 2011 Nov 4;10:97. PubMed PMID: 22054019.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Azelnidipine prevents cardiac dysfunction in streptozotocin-diabetic rats by reducing intracellular calcium accumulation, oxidative stress and apoptosis. AU - Kain,Vasundhara, AU - Kumar,Sandeep, AU - Sitasawad,Sandhya L, Y1 - 2011/11/04/ PY - 2011/07/15/received PY - 2011/11/04/accepted PY - 2011/11/8/entrez PY - 2011/11/8/pubmed PY - 2012/4/4/medline SP - 97 EP - 97 JF - Cardiovascular diabetology JO - Cardiovasc Diabetol VL - 10 N2 - BACKGROUND: Numerous evidences suggest that diabetic heart is characterized by compromised ventricular contraction and prolonged relaxation attributable to multiple causative factors including calcium accumulation, oxidative stress and apoptosis. Therapeutic interventions to prevent calcium accumulation and oxidative stress could be therefore helpful in improving the cardiac function under diabetic condition. METHODS: This study was designed to examine the effect of long-acting calcium channel blocker (CCB), Azelnidipine (AZL) on contractile dysfunction, intracellular calcium (Ca2+) cycling proteins, stress-activated signaling molecules and apoptosis on cardiomyocytes in diabetes. Adult male Wistar rats were made diabetic by a single intraperitoneal (IP) injection of streptozotocin (STZ). Contractile functions were traced from live diabetic rats to isolated individual cardiomyocytes including peak shortening (PS), time-to-PS (TPS), time-to-relengthening (TR90), maximal velocity of shortening/relengthening (± dL/dt) and intracellular Ca2+ fluorescence. RESULTS: Diabetic heart showed significantly depressed PS, ± dL/dt, prolonged TPS, TR90 and intracellular Ca2+ clearing and showed an elevated resting intracellular Ca2+. AZL itself exhibited little effect on myocyte mechanics but it significantly alleviated STZ-induced myocyte contractile dysfunction. Diabetes increased the levels of superoxide, enhanced expression of the cardiac damage markers like troponin I, p67phox NADPH oxidase subunit, restored the levels of the mitochondrial superoxide dismutase (Mn-SOD), calcium regulatory proteins RyR2 and SERCA2a, and suppressed the levels of the anti-apoptotic Bcl-2 protein. All of these STZ-induced alterations were reconciled by AZL treatment. CONCLUSION: Collectively, the data suggest beneficial effect of AZL in diabetic cardiomyopathy via altering intracellular Ca2+ handling proteins and preventing apoptosis by its antioxidant property. SN - 1475-2840 UR - https://www.unboundmedicine.com/medline/citation/22054019/Azelnidipine_prevents_cardiac_dysfunction_in_streptozotocin_diabetic_rats_by_reducing_intracellular_calcium_accumulation_oxidative_stress_and_apoptosis_ L2 - https://cardiab.biomedcentral.com/articles/10.1186/1475-2840-10-97 DB - PRIME DP - Unbound Medicine ER -