OBJECTIVETo study the effects of rhynchophylline, isorhynchophylline, and rhynchophylla alkaloids on the vascular adventitial fibroblasts (VAF) apoptosis and proliferation in thoracic aorta of spontaneously hypertensive rats (SHR), and on the Bcl-2, Bax, c-Fos, c-Myc, laminin (LN), and fibronectin (FN).

METHODSForty 8-week old male SHR were randomly divided into five groups, i. e., the model group, the captopril group (17.5 mg/kg), the isorhynchophylline group (5.0 mg/kg), the rhynchophylline group (5.0 mg/kg), and the rhynchophylla alkaloids group (50.0 mg/kg), 8 in each group. In addition, eight 8-week old male Wistar rats were selected as the normal group. Equal volume of normal saline was given to rats in the normal group and the model group by gastrogavage. Rats in the rest groups were perfused with isovolumic medication solution (10 mL/kg), six days per week for eight successive weeks. The dosage of drugs was adjusted according to the change of body weight. The VAF apoptosis rate of the thoracic aorta was measured by Annexin V-FITC combined with PI dyeing and flow cytometry. The protein expressions of thoracic aortic Bcl-2, Bax, c-Myc, c-Fos, FN, and LN were detected by immunohistochemical assay. The adventitial transforming growth factor beta1 (TGF-beta1) mRNA expression in the thoracic aorta was detected by in situ hybridization method.

RESULTSCompared with the model group, the tail arterial systolic pressure decreased, the VAF apoptosis and the protein expression of Bax increased, Bcl-2, c-Fos, FN, LN, and TGF-beta1 mRNA all decreased in the thoracic aorta of SHR in each treatment group after 4-and 8-week of intervention. Rhynchophylline, isorhynchophylline, and rhynchophylla alkaloids could inhibit the protein expression of c-Myc with statistical difference (P<0.05, P<0.01). Compared with the captopril group, there was no statistical difference in decreasing the tail arterial systolic pressure, the protein expression of c-Fos and the mRNA expression of TGF-beta1 among the rhynchophylline group, the isorhynchophylline group, and the rhynchophylla alkaloids group (P>0.05). There was statistical difference in increased VAF apoptosis and decreased protein expressions of Bcl-2, c-Myc, and LN (P<0.05, P<0.01). There was statistical difference in increased protein expression of Bax between the rhynchophylline group and the isorhynchophylline group (P<0.05, P<0.01). There was statistical difference in decreased protein expression of FN in the isorhynchophylline group (P<0.05). There was no significant difference among the rhynchophylline group, the isorhynchophylline group, or the rhynchophylla alkaloids group (P>0.05).

CONCLUSIONSRhynchophylline, isorhynchophylline, and rhynchophylla alkaloids might promote the VAF apoptosis in the thoracic aorta of SHR by regulating the protein expressions of Bcl-2 and Bax. They might inhibit the VAF proliferation by restraining protein expressions of c-Fos, c-Myc, and TGF-beta1 mRNA. They also might improve the thoracic aorta wall reconstruction and decrease the tail arterial systolic pressure by down-regulating the protein expressions of FN and LN, and attenuating the deposition of extracellular matrix.