Effects of site-specific antibody of Na+-Ca2+ exchanger on isolated rat heart functions/vascular tone and comparison with ouabain and (±)Bay K8644

AIM：To investigate the effects of site-specific (α-1 repeat: 124HNFTAGDLGPSTIVGSAAFNMF145) antibody of Na+-Ca2+ exchanger (NCX) on the isolated rat heart functions and vascular tone and to compare them with the effects of Na+-K+ pump inhibitor ouabain and L-type Ca2+ channel agonist (±)Bay K8644. METHODS：The heart and thoracic aorta were rapidly isolated from the adult rats weighing 250～300 g. The hemodynamic indexes including left ventricular developed pressure, maximal rate of rise/decline of left ventricular pressure (±dp/dtmax) and coronary resistance were observed by Langendorff isolated heart perfusion system. The rings of thoracic aorta were mounted into the organ baths and the vascular tone was determined. RESULTS：At concentrations of 10, 20 and 40 nmol/L, the site-specific antibody of NCX enhanced the cardiac functions in a dose-dependent manner during the perfusion period with no arrhythmia. At the same time, it did not increase the coronary resistance. The antibody had no effect on the vascular tone of isolated thoracic aorta ring at the same concentrations. Ouabain at concnentration of 0.5 mmol/L and (±)Bay K8644 at concentration of 01 mmol/L had similar effects with the site-specific antibody of NCX at concentration of 40 nmol/L on left ventricular developed pressure and +dp/dtmax of isolated rat hearts during perfusion, but (±)Bay K8644 (01 mmol/L) didn’t have significant effect on -dp/dtmax. Ouabain (0.5 mmol/L) even reduced -dp/dtmax as compared with the control. After administration of ouabain (0.5 mmol/L) for 5 min, most isolated hearts appeared premature pulse more than 5 beats/min. (±)Bay K8644 (0.1 mmol/L) did not induce arrhythmia during all the time of exposure. CONCLUSION: The site-specific (α-1 repeat: 124HNFTAGDLGPSTIVGSAAFNMF145) antibody of NCX enhances both systolic and diastolic functions of isolated rat hearts without arrhythmia. Meanwhile, this antibody doesn’t increase coronary resistance during perfusion and vascular tone in isolated thoracic aorta rings.