Matrix is the site of indirect effects of propranolol on the ion channelopathies in cardiac remodeling by L-thyroxine.
Cardiac remodeling by chronic L-thyroxine medication causes exaggerated cardiac arrhythmias in relation to ion channelopathies that involve multichannels. The matrix of lipid membrane is likely the key site where channel lesions, possibly will develop and be benefitted by drug intervention. Cardiac remodeling in rats and guinea pigs was developed by L-thyroxine 0.5 mg/kg SC for 10 days. Propranolol was instituted on days 8-10. Whole cell holding was applied to measure ion currents. An increase in HR, dispersion of QTc, mitochondrial Na+/K+ ATPase, Ca2+/Mg2+ ATPase, and LPO production were found in the model. T3 and T4 levels in plasma were high. Propranolol was effective in regressing cardiac remodeling, together with lowering all the parameters and the enhanced I(Ca.L),I(KS), and I(KR) currents, but T3 and T4 remained basically unchanged. The changes in ion channels are likely the consequence of the cardiac remodeling that is formed by oxidative stress and increased energy consumption provoked by L-thyroxine. The benefit of propranolol on the disordered ion channels is mediated by its ability to ameliorate lesions of the matrix.
Dai
De-Zai
DZ
Research Division of Pharmacology, China Pharmaceutical University, Nanjing, China. njpdaidz@jlonline.com
Wang
Hong-Lan
HL
Zhang
Guang-Qin
GQ
He
Gou-Xing
GX
Chen
Li
L
D000465:Algorithms; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000517:prevention & control; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D003196:Computer Graphics; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism*; D008564:Membrane Potentials; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013963:Thyroid Hormones; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000502:physiology
D000889:Anti-Arrhythmia Agents; D008563:Membrane Lipids; D013963:Thyroid Hormones; D014284:Triiodothyronine; D011433:Propranolol; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D013974:Thyroxine