Electrophysiologic Effects Of 17-β-Estradiol On Pacemaker Cells In Sinoatrial Nodes Of Rabbits

The investigation of epidemiology showed: there was a significantly sex difference of cardiovascular diseases in the morbidity and the mortality. The morbidity, which in women was significantly lower than men in cardiovascular diseases, before menopause; but the morbidity and the mortality of the cardiovascular diseases were obviously rising, when ovary was cut or after menopause, it was as same as the same men. Estrogen was a kind of steroid parahormones, which had a extensived bioactivity. 17-β-estradiol (Est) was a main component of estrogen, it possessed widely biology effects in body. Est had many protective effect in cardiovascular. The experiment had been proved: it could cut down angiotasis and fat in the blood; anti-oxidation and protected blood vessel endothelium; promoted vascular endothelial cell synthesized NO; inhibited platelet adhesion reaction and aggregation; inhibited the production of endothelin and adherence factor; further inhibited myocardial damage; prevented slow calcium channel in the vascular smooth muscle cell, inhibited the generation, immigration and the extracellular matrix of the vascular smooth muscle cell, thus suppressing atherogenesis, urged the fadeaway of the plaque; anti-anticoagulated blood and anti- fibrolysis. But in recently years, it did not confirm the effects of estrogen replacement therapy (HRT) in the large-scale clinical trial, contradicting, it could increase the dangers of cardiovascular diseases. In our previous studies, we found Est could inhibit the contraction and prolong action potential duration and effective refractory period in papillary muscles of guinea pig. We also found that Est inhibited inward rectifier and delayed rectifier K+ currents in guinea pig ventricular myocytes, which might be the one mechanism of Est antiarrhythmia. Up to now, little is known about the effects of Est on electrophysiology of SA node and underlying mechanisms. In the present study, we observed the electrophysiological effects of Est on SA node and investigated the underlying mechanism in physiological and simulated ischemic condition by using intracellular microelectrode technique.1. Electrophysiological effects of Est on pacemaker cells in SA nodes of rabbits in physiological conditionThe cardiac electrophysiological effects of Est were examined on pacemaker cells in sinoatrial nodes of rabbits using intracellular microelectrode technique. The results obtained are as follows:1.1 Est (1, 10, 100μmol/L) not only significantly decreased the amplitude of action potential (APA), maximal rate of depolarization (Vmax), decreased the velocity of diastolic (phase 4) depolarization (VDD), rate of pacemaker firing (RPF), but also prolong the duration of 50% (APD50) and 90% repolarization of action potential (APD90) in concentration dependent manner. At 100μmol/L concentration, APA and Vmax decreased from 68.7±6.8 mv and 4.8±0.4 v/s to 60.3±6.5 mv and 3.0±0.8 v/s (P<0.05-0.01), respectively. VDD and RPF decreased from 61.3±9.2 mv/s and 169.9±13.6 beat/min to 33.6±12.2 mv/s and 136.8±23.6 beat/min (P<0.01), APD50 and APD90 prolonged from 92.7±2.2 and 127.8±5.1 ms to 124.3±5.0 and 153.4±12.8 ms (P<0.01), respectively.1.2 Tamoxifen (10μmol/L), an inhibitor of estrogen nuclear receptor, did not affect the electrophysiological effects of Est (10μmol/L) on SA node cells.1.3 NG-nitro-L-arginine methyl ester (L-NAME, 100μmol/L), a nitric oxide (NO) synthase inhibitor, completely abolished the electrophysiological effects of Est (10μmol/L) on SA node cells.The above results suggested that Est inhibited the electrophysiological activity on pacemaker cells in rabbit SA node dose-dependently through a non-genomic mechanism related with NO.2. Effects of 17-β-Estradiol on electric activity in SA node pacemaker cells of rabbit during simulated ischemiaThe cardiac electrophysiological effects of Est were examined on pacemaker cells in sinoatrial node of rabbits during simulated ischemia using intracellular microelectrode technique. The results obtained are as follows: 2.1 During simulated ischemia, APD50 and APD90 decreased from 90.4±4.9 and 127.6±7.9 ms to 70.6±6.8 and 104.8±9.3 ms (P<0.01), RPF decreased from 159.8±6.9 to 113.6±10.5 beat/min (P<0.01), VDD decreased from 57.7±5.9 to 25.5±5.5 mv/s (P<0.01).2.2 Est (10μmol/L) could block the effects of simulated ischemia on the AP.2.3 Tam (10μmol/L) had no effect on the effects of Est (10μmol/L) during simulated ischemia.The above results suggested that Est could protect the heart against the change of electrophysiological activity induced by simulated ischemia.