The Effect Of NXT On Myocardium And Vessels' Remodeling In Spontaneously Hypertensive Rats

Objective1. To observe the effects of Nao Xin Tong (NXT), one of Chinese traditional herbal composition, on the remodeling of myocardium and vessels in spontaneously hypertensive rats(SHR).2. To evaluate the expression of L-VOCC(CaVα1C),SERCA-2a-,IP3R-1 and RyR-3 in heart and thoracic aorta under the treatment of NXT, and reveal the potential pathophysiological mechanism in the myocardium and vessels'remodeling.MethodsPartⅠThirty-two twelve-week-old male SHR were randomized into high-dose NXT treated group(NH group, 1.5 g.kg-1.d-1, n=8), low-dose NXT treated group(NL group, 0.5 g.kg-1.d-1, n=8), losartan treated group(LOS group, 30 mg.kg-1.d-1, n=8) and distilled water control(SHR group, n=8). And Wistar-Kyoto rats(WKY group, n=8) were served as normal control. The former three groups were administered for 12 weeks by gavage in mixture with 2 mL distilled water, SHR and WKY control were given the same amount of distilled water. Systolic blood pressure was examined by the tail-cuff method. Wet weight of left ventricle to body weight ratio(LVM/BW) was assessed on sacrifice. Myocardial collagen fibers in the sections were observed under light microscope. The wall-to-lumen area ratios of thoracic aorta and mesenteric arteries(3th branch) were calculated.PartⅡThe mRNA levels for L-VOCC(CaVα1C),SERCA-2a-,IP3R-1 and RyR-3 in heart and thoracic aorta were detected by RT-PCR. The amount and distribution of L-VOCC(CaVα1C) and SERCA-2a protein were determined by immunohistochemistry. SERCA-2a protein expression was measured by Western Blot.ResultsPartⅠ1. After 12 weeks treatment with high-dose and low-dose NXT, systolic blood pressure in both groups was markedly lower than that in SHR control group (P<0.01 vs SHR), but no significant difference was found between the two groups. Systolic blood pressure in high-dose NXT group, was slightly, but statistically significantly, decreased after treatment than that before treatment (P<0.01 vs before treatment), while no marked difference in low-dose treated group was found.2. Myocardial collagen volume fraction in the interstitial, endocardial and perivascular area was significantly reduced by the treatment with NXT (P<0.01 vs SHR), whereas no significance was found between the two groups.3. In thoracic aorta, the wall area to lumen area ratio in SHR group was markedly higher than that in high-dose NXT group and low-dose NXT group (P<0.01 vs SHR), but no significant difference was found between the two groups.4. In mesenteric arteries(3th branch), the wall-to-lumen area ratio was significantly reduced in high-dose NXT group than in SHR group (P<0.01 vs SHR), while no marked difference in low-dose NXT treated group was found.PartⅡ1. Compared with SHR group, CaVα1C mRNA and protein in high-dose NXT group was obviously decreased (P<0.05 vs SHR), while in low-dose NXT treated group no marked difference was showed in left ventricle.2. The mRNA and protein of SERCA-2a in high-dose group and low-dose group were reduced significantly in comparison with SHR group (P<0.01 vs SHR), but there was no marked difference between the two groups in left ventricle. 3. In IP3R-1 transcription level, there was no significant difference between the two group in left ventricle.4. RyR-3 mRNA in high-dose group and low-dose group were all downregulated significantly than in SHR group (P<0.01 vs SHR), whereas no significance was found between the two group in left ventricle.5. In thoracic aorta, there was no significant difference for L-VOCC(CaVα1C),SERCA-2a-,IP3R-1 and RyR-3 with NXT.Conclusions1. NXT may prevent the development of arterial blood pressure in SHR.2. NXT may inhibit cardiac collagen fibers accumulating.3. NXT could attenuate the vessels hypertrophy in SHR.4. The expressions of calcium regulatory protein such as L-VOCC(CaVα1C),SERCA-2a,IP3R-1 were abnormal in myocardium and vascular smooth muscle.5. The abnormal expression of calcium regulatory protein may be the important factor for myocardial hypertrophy and fibrosis.6. NXT may ameliorate calcium channels, L-VOCC(CaVα1C),SERCA-2a and IP3R-1, remodeling in myocardium.