| Essential hypertension(EH) is one of the most common cardiovascular disease, which can cause lesion of heart,encephalon and kidney. Left ventricular hypertrophy(LVH) is regarded as an independent dangerous factor which predicts a high incidence of coronary heart disease,symptomatic congestive heart failure and cerebral apoplexy. So regression of left ventricular hypertrophy has been the important role of different antihypertensive drugs.The pathological basis of left ventricular hypertrophy include myocytes hypertrophy and cardiac fibroblast(CFs) proliferation and excessive collagen synthesis in CFs,which leads to extracellular interstitial accumlation of collagen,and affect the progression of LVH. Carvedilol, an effective third β-adrenoceptor antagonist,can provide β1, β2 and α1 adrenoceptor blocking avtivity. It has been proved that carvedilol can reduce left ventricular mass, and to date, whether carvedilol is involved in the modulating mechanism of proliferation and collagen synthesis of CFs is still unclear. In the study we cultured CFs derived from SHR and Wistar rats,the aim was to investigate the effects of carvedilol,bisoprolol and prazosin on CFs proliferation and collagen synthesis and proliferating cell nuclear antigen(PCNA) expression in CFs, as well as observed the activity of NOS-NO system and its relationship with CFs proliferation and collagen synthesis,so as to elucidate the cellular andmolecular mechanisms for regression of LVH in EH and provide new theoretical evidence of prevention and treatment for LVH.In this study, SHR and Wistar rats were used as experiment model, 3H-proline incorporation was adopted to determine collagen synthesis,3H-TdR incorporation to determine DNA synthesis, modified MTT array to determine cell number.Nitric acid reductase method to detect NO contents, spectrophotometry was used to determine NOS activity,immunity chemical coloration technique was used to analyze PCNA protein expression. We observed dynamically: (1) under basal condition, the changes of MTT OD value,DNA synthesis and collagen synthesis and the avtivity of NOS-NO system in CFs of SHR and Wistar rats; (2) the effects of carvedilol on CFs collagen synthesis and proliferation induced; (3) the effects of carvedilol on the activity of NOS-NO system; (4) the effects of bisoprolol on CFs collagen synthesis and proliferation;(5) the effects of prazosin on CFs collagen synthesis and proliferation induced; (6)the effects of carvedilol on PCNA protein expression in CFs nuclear .The results shows :(1)Under basal condition, the incorporation of 3H-proline (1196.8 ±71.5cpm), the incorporation of 3H-TdR (606.0 ±54.7 cpm) and A570 value by MTT assay(0.38±0.01) in CFs derived from SHR were obviously greater than those of Wistar rats(795.4±61.1cpm,495.2±49.8cpm, 0.36±0.01), which were practical in statistics(both P<0.01). (2)With the increase of carvedilol(10-8~10-5M)concentration, 3H-Proline incorporation in wistar rats group were (716.0 ± 50.3cpm,609.0±49.2cpm,457.8±44.7cpm and 408.2 ± 38.0 cpm), respectively. The incorporation in SHR group were(1055.0±54.8cpm, 832.4±64.6cpm,604.2 ± 39.7cpm and 480.8± 30.3cpm),respectively. With the increase of carvedilol (10-8~10-5M) concentration, 3H-TdR incorporation in wistar rats group were(462.2±40.1 cpm, 388.2±35.0cpm, 322.6 ± 32.7cpm and 277.8 ±25.3cpm), respectively. The incorporation in SHR group were(554.0±52.2 cpm, 452.0± 35.9cpm, 317.2±36.2cpm and 279.6±24.7cpm), respectively. With the increase of carvedilol concentration, 3H-Proline and 3H-TdR incorporation of CFs derived from two group decreased significantly. (3) Withtreatment of 10-8~10-5M carvedilol,as contrast to control group(100%), 3H-Proline incorporation in wistar rats group were (90.0 ± 6.2 % , 76.8 ± 6.0 %, 57.6 ±5.5% and 51.4±4.9%),respectively. The incorporation in SHR group were (88.0 ± 4.5%, 69.6±5.5%, 50.6±3.4% and 40.2±2.3%),respectively.Between 10-6M and 10-5M carvedilol groups,there were obvious difference in the incorporation,which we... |
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