Depressive effect on proliferation of vascular smooth muscle cells by tetrandrine in hypertensive rats / 中国药理学与毒理学杂志

ABSTRACT

To analyse the effect of tetrandrine(Tet) on proliferation of aortic vascular smooth muscle cells ( AVSMC), AVSMC were isolated and cultured from sham-operated rats(Sham), renovascular hypertensive rats〔RHR, 18 weeks after two kidney one clip(2K1C) operation〕, and Tet (50 mg*kg-1*d-1 po for 9 weeks from week 9 after 2K1C operation)treated RHR. The proliferation of AVSMC was detected by MTT method, and the DNA synthesis was evaluated by ［3H］-thymidine incorporation. The results showed that ①The ultrastructure of aorta suggested that AVSMC in RHR had transferred from contractile phenotype to synthetic phenotype; ②Compared to Sham, AVSMC from RHR showed a higher proliferative property with a higher cell number and an increased growth rate stimulated by norepinephrine(NE) or angiotensinⅡ(AngⅡ); ③Compared to untreated RHR, AVSMC from Tet treated RHR showed a reduced reactivity to NE- or AngⅡ-stimulated proliferation and growth rate; ④Tet(0.1－10 μmol*L-1) treated in vitro induced a concentration-dependent depression in ［3H］ thymidine-incorporation stimulated by NE or AngⅡ in AVSMC from either RHR or Sham. This study provides an evidence of increased reactivity to NE or AngⅡ in AVSMC of RHR. Tet inhibits the proliferation and DNA synthesis in AVSMC, depresses the susceptibility of AVSMC to AngⅡ and NE, both contribute to the regression effect on hypertensive vascular remodeling.