Inhibition of Tanshinone Ⅱ A on cardiac aldosterone synthesis and relevant genic expression in hypertension

Chengye ZHAN; Xiuliang TAO; Shaojie HAN; Zhi ZHENG

ABSTRACT

BACKGROUND:

Aldosterone is main pathogenic factor of left ventricular hypertrophy, for which, to inhibit its biosynthesis effectively may prevent and treat hypertension induced by left ventricular hypertrophy.

OBJECTIVE:

To investigate the effects of Tanshinone Ⅱ A on myocardiac aldosterone synthesis and expression of its relevant genic CYP11B1and CYP1 1B2 in spontaneously hypertensive rats(SHR) and explore the possi ble nechanism of Tanshinone Ⅱ A on inhibiting hypertension induced by left ventricular hypertrophy.

DESIGN:

SHR were employed as the objects in the experiment and WKY rats with normal blood pressure (WKY rats) were employed in the controlgroup. Complete group division and randomized control experiment was designed. Analysis of variance was used for the means comparison among groups.

SETTING:

Department of Emergency and Institute of Integrated Traditional Chinese and Western Medicine in Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology.MATERIALSThe experiment was performed in the laboratory of Department of Emergency in Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from January 2003 to February 2004, in which, 10 male WKY rats with normal blood pressure of 12-week-old were employed in the control group and 20 male SHR of 12-week-old were randomized into two groups, named hypertension group and Tanshinone ⅡA group, 10 rats each group.

METHODS:

In Tanshinone Ⅱ A group, Tanshinone Ⅱ A 1.5 mg/kg was injected abdominally everyday. The distilled water of same volume was injected abdominally in hypertension group and the control group. Twelve weeks after experiment, myocardial specimens were collected after rats sacrificed. Radioimmunoassay was used to determine the contents of aldosteron and angiotensin Ⅱ in myocardial tissue and reverse transcriptase polymerase chain reaction (RT-PCR) were used to measure mRNA level of CYP11B1 and CYP11B2 genes relevant to aldosterone synthesis.MAIN OUTCOME

MEASURES:

Contents of aldosterone and angiotensin Ⅱ in myocardial tissue and mRNA expression of CYP11B1 and CYP1 1B2 genes.

RESULTS:

All of 20 SHR and 10 WKY rats entered result analysis. ① Myocardial aldosterone content of rats in 12 weeks after experiment that in hypertension group and Tanshinone Ⅱ A group was higher remarkably than that in the control group [(0.056±0.014), (0.031±0.010), (0.018±0.009) ng/g,P ＜ 0.01, 0.05]; that in Tanshione Ⅱ A group was lower remarkably than that in the hypertension group (P ＜ 0.05). ② Myocardial angiotension Ⅱ content of rats in 12 weeks after experiment that in the hypertension group and Tanshinone ⅡA group was higher remarkably than that in the control group [(0.093±0.016), (0.088±0.024), (0.043±0.012) ng/L, P ＜ 0.01]. ③ Expression of CYP11B1 gene in myocardial tissue of rats in 12 weeks after experiment that in the hypertension group and Tanshinone Ⅱ A group was higher remarkably than that in the control group (2.774±0.138, 2.533 ±0.127, 1.973±0.102, P ＜ 0.05). ④Expression of CYP11B2 gene in myocardial tissue of rats in 12 weeks after experiment; that in the hypertension group and Tanshinone ⅡA group was higher remarkably than that in the control group (1.573±0.106, 1.024±0.113, 0.786±0.121, P ＜ 0.01,0.05); that in the Tanshinone ⅡA group was lower remarkably than that in the hypertension group (P ＜ 0.05). ⑤The electrophoresis band positions of myocardial CYP11B1 and CYP11B2 as well as RT-PCR products of glyceraldehydes-3-phosphate dehydrogenase (GAPDH), the consulting gene,were in conformity with the theoretic values.

CONCLUSION:

The inhibition of Tanshinone Ⅱ A on hypertension induced by left ventricular hypertrophy is probably contributed to its downregulating effect on myocardiac CYP11B2 gene expression relevant to aldosterone synthesis and to its reducing action on local biosynthesis of aldosterone in heart.