Title of article :
Exploring the role of dimethylarginine dimethylaminohydrolasemediated reduction in tissue asymmetrical dimethylarginine levels in cardio-protective mechanism of ischaemic postconditioning in rats
Author/Authors :
Kaur, Kamaldeep Department of Pharmaceutical Sciences and Drug Research - Punjabi University - Patiala, India , Singh, Nirmal Department of Pharmaceutical Sciences and Drug Research - Punjabi University - Patiala, India , Dhawan, R. K. Department of Pharmacology - Khalsa College of Pharmacy - Amritsar, India
Abstract :
Objective(s): Reperfusion of ischaemic myocardium results in reduced nitric oxide (NO)
biosynthesis by endothelial nitric oxide synthase (eNOS) leading to endothelial dysfunction and
subsequent tissue damage. Impaired NO biosynthesis may be partly due to increased levels of
asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of eNOS. As dimethylarginine
dimethylaminohydrolase (DDAH) is a key enzyme responsible for degradation of ADMA, the present
study was designed to explore the role of DDAH/ADMA/NO pathway in cardio-protective mechanism
of ischaemic postconditioning.
Materials and Methods: Isolated rat hearts were subjected to myocardial ischaemia for 30 min
followed by reperfusion for 2 hours in control group. Myocardial injury was assessed by measurement
of infarct size, left ventricular developed pressure (LVDP), lactate dehydrogenase (LDH) and creatine
kinase (CK) enzymes in coronary effluents. The reperfused hearts were homogenised and tissue
concentration of nitrite, ADMA level and DDAH enzyme activity was determined.
Results: A significant increase in infarct size, LDH, CK release in coronary effluents and ADMA
level in myocardial tissue was observed in control group. The increase in tissue ADMA coincided
with reductions of NO tissue concentrations and DDAH activity. Ischaemic postconditioning
significantly attenuated ischaemia-reperfusion induced myocardial injury manifested in the terms of
decreased infarct size, LDH, CK, tissue ADMA along with increase in NO levels and DDAH enzyme
activity. Pretreatment with L-Homocysteine (300 μM), a competitive inhibitor of DDAH, and L-NGnitroarginine
methyl ester (L-NAME; 100 μM), an inhibitor of eNOS, completely abolished ischaemic
postconditioning-induced myocardial protection.
Conclusion: Enhancing DDAH activity by postconditioning may be a novel target to reduce ADMA level
and increase NO bioavailability to prevent myocardial ischaemia-reperfusion injury.
Keywords :
ADMA , DDAH , Nitric oxide , Postconditioning , Myocardial ischaemia reperfusion injury
Journal title :
Astroparticle Physics