The Mechanism Of Aortic Vascular Remodeling In DOCA-salt Hypertensive Rats

Objective: To observe the influence of bosentan, enalapril and nifedipine on aortas of DOCA-salt hypertensive rats (DHR), and investigate the mechanism of aortic vascular remodeling in DHR.Method: 28 male sprague-dawley rats were unilaterally nephrectomized, given penicillin 2 x 104u/Kg three days. Survived 25 rats were randomly divided into 5 groups. One group served as control group, drinking tap water. Four other groups were administered DOCA subcutaneously (50mg/kg/week) and 1%saline was added to their tap water for drinking. Simutaneously, they were given placebo, bosentan 100mg/kg/day, enalapril 20mg/kg/day, and nifedipine 35 mg/kg/day. Systolic blood pressure (SBP) was measured by tail-cuff methods every week. After 4 weeks treatment, the rats were killed by decapitation. Aortas were dissected, A-0.5-cm-long segment of aorta adjacent the heart was used as histologic study, preserved in 10% formalin ,embedded in paraffin, cut at 4um and stained with hematoxylin and eosin; The remnant aortic segment was then snap-frozen in liquid nitrogen and stored at -70℃.Histologic study of the aorta was examined using light microscope, measuring aortic media thickness (MT) and luminen.Results: SBP of placebo group were ascending, attaining 178± 5mmHg 4 weeks ago. Daily adminitration of bosentan blunted SBP increasing, attaining 152±4mmHg 4 weeks ago. Enalapril had no influence on SBP, while nifedipine could normalize SBP of DHR. AorticMT of placebo group was thicker than control group, and aortic vascular remodeling was significant. Bosentan could lessen aortic MT, and alleviated aortic VR. Enalapril and nifedipine had no influence on aortic VR. Expression of ET-lmRNA in aorta was increased four times in placebo group than in control. Bosentan , Enalapril and nifedipine had no influence on aortic ET-1RNA expression of DHR. There was no significant difference among them.Conclusion: There was significant vascular remodeling in DHR. Bosentan could blunt SBP increasing slightly but significantly, and alleviate vascular remodeling, but could not affect ET-lmRNA expression in aorta of DHR. Nifedipine could depress SBP increasing, but have no effect on aortic vascular remodeling . Enalapril had no influence on SBP or aortic vascular remodeling. Enalapril and Nifedipine had no influence on aortic ET-lmRNA expression. ET-lmRNA was overexpressed in arota of DHR, and increased ET-1 can result in vascular smooth muscle cell hypertrophy and mitogenesis through ETA and ETB receptors. Increased ET-1 in aortic tissue is main reason of vascular smooth muscle cell hypertrophy and mitogenesis, which lead to widening aortic MT.