Abstract: Objective To investigate the expression of gap junction protein Cx43 in the cardiac muscle of spontaneous hypertensive rat and the effects of various antagonists against renin angiotensin aldosterone system (RAAS) on Cx43 expression. Methods 70 spontaneous hypertensive rats of 8-week age, 200-gram weight were separated into 7 groups, as hypertension, ramipril, telmisartan, eplerenone, ramipril+telmisartan, telmisartan+eplerenone, and ramipril+eplerenone treatment group. Another 10 healthy Wistar rats of the same age and weight were used as control group. All the rats were given intragastric administration at 8 a.m. every morning, and measured arteria caudilis pressure at 0, 4 and 8 week, respectively. 8 weeks later, all the rats were sacrificed, and the hearts were taken to measure the weight of left ventricle and the ratio of left ventricle to body weight. Myocardial fibrosis was observed by H&E staining of paraffin embedded sections, and Cx43 expression was examined by RT-PCR and western blot. Results The arteria caudilis pressure of spontaneous hypertensive rats was significantly higher than that of healthy control Wistar rats (P<0.01). The decreased blood pressure was observed in RAAS antagonists treated rats, compared with hypertension group (P<0.05). The combined treatment of telmisartan and eplerenone had the best effect of lowering blood pressure. Moreover, the weight of left ventricle, the ratio of left ventricle to body weight, myocardial fibrosis and angiotensin Ⅱ were all prominently decreased in telmisartan and eplerenone combination group (P<0.01). The expression of Cx43 in spontaneous hypertensive rats was significantly lower than that of healthy control Wistar rats (P<0.01). Increased Cx43 expression was observed in RAAS antagonists treated rats, compared with hypertension group (P<0.05). Conclusion The expression of gap junction protein Cx43 was significantly down-regulated in spontaneous hypertensive rats, while RAAS antagonists increased Cx43 expression. The combination of telmisartan and eplerenone effectively recovered the expression of Cx43 and probably reversed hypertension.