[Effect of cyclosporine A on myocardial calcineurin activity of the right ventricle and plasma NO, nitric oxide synthase and endothelin-1 levels in rats with chronic hypoxia].

Abstract

OBJECTIVE:

To study the role of calcineurin in the progression of right ventricle myocardial hypertrophy in rats exposed to chronic hypoxia by examining the effect of Ca(2+) channel blockers on the activation of calcineurin and plasma levels of nitric oxide (NO), NO synthase, and endothelin-1 (ET-1).

METHODS:

Rat models of right ventricle myocardial hypertrophy were established by exposing the rats to chronic hypoxia in 10.0%+/-0.5% O(2) for 7 d. The 24 rat models were assigned into normoxic group, hypoxic group and cyclosporin A (CsA)-treated hypoxic group. The rats in normoxic group were kept under normoxic environment, while those in the other 2 groups were subjected to further hypoxic treatment for 14 d, with the rats in CsA group receiving intraperitoneal CsA injection at 20 mg/kg on a daily basis. On day 21 of the experiment, all the rats were killed to collect the hearts for measuring the weight ratio of the right ventricle to the left ventricle and interventricular septum [RV/ LV+S ], as well as the right ventricle to body weight ratio (RV/BW); blood samples were also drawn from the ventricles for measuring plasma NO, iNOS, and ET-1 levels, with the ventricular myocardial [Ca(2+)](i) and the activity of calcineurin also determined.

RESULTS:

The RV/(LV+S) and RV/BW were significantly higher in hypoxic group than those of the normoxic and CsA groups (P<0.01); the right ventricular myocardial [Ca(2+)](i) in CsA group was significantly higher than that in the other two groups (P<0.01). In comparison with the normoxic group, the right ventricular myocardial calcineurin activity was significantly increased in the hypoxic group. CsA treatment significantly suppressed calcineurin activity (P<0.01).

CONCLUSIONS:

Calcineurin possibly plays a role in the progression of right ventricle myocardial hypertrophy in rats with chronic hypoxia. Blocking L-type Ca(2+) channels with CsA effectively prevents the development of myocardial hypertrophy possibly by inhibiting calcium influx and suppressing calcineurin activity.

• Authors: Jian-xin Tan, Chen-zhou Liu, Yu-li Jie, You Wang, Yu-ge Huang
• Journal: Di 1 jun yi da xue xue bao = Academic journal of the first medical college of PLA (Di Yi Jun Yi Da Xue Xue Bao) Vol. 24 Issue 6 Pg. 656-8 (Jun 2004) ISSN: 1000-2588 [Print] China
• PMID: 15201082 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Endothelin-1
• Immunosuppressive Agents
• Nitric Oxide
• Cyclosporine
• Nitric Oxide Synthase
• Calcineurin

Topics

• Animals
• Calcineurin (analysis)
• Chronic Disease
• Cyclosporine (pharmacology)
• Endothelin-1 (blood)
• Female
• Hypoxia (metabolism)
• Immunosuppressive Agents (pharmacology)
• Male
• Myocardium (chemistry)
• Nitric Oxide (blood)
• Nitric Oxide Synthase (blood)
• Rats