Study of Right Ventricular Hypertrophy in Experimental Pulmonary Hypertension

实验性肺动脉高压右心室肥厚的研究

• 批准号: 01570489
• 负责人: HONDA Masaaki
• 金额: $ 0.64万
• 依托单位: Shimane Medical Univeristy
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-01570489/
• 关键词: Cardiac hypertrophy; Myosin isoenzymes; Collagen; ACE inhibitor; Calcium antagonist; Monocrotaline; Beta-receptors; Pulmonary hypertension; Collagen type; Collagen content; cardiac hypertrophy; myosin isoenzymes; adrenergic receptors; collage

OBJECTIVES : Myosin and collagen are major components of the heart. In has been revealed that when the heart receives pressure overload, not only contractile proteins but also collagen metabolisms change quantitatively and qualitatively. However, relative changes in contractile and non-contractile protein metabolisms in cardiac hypertrophy are not clarified simultaneously, and its meaning remains unclear. Moreover, beta-receptors, which are closely related to cardiac function, are known to change during the development of cardiac hypertrophy. In this study, we examined the above-mentioned parameters of pressure-overloaded and nonpressure-overloaded ventricles simultaneously. We also examined the effects of antihypertenive drugs on the above-mentioned parameters of hypertrophied heart and analyzed merits and demerits of these antihypertensive agents from the view points of contractile and noncontractile protein metabolisms. MATERIALS & METHODS : Monocrotaline-induced right ventricular h … More ypertrophy(RVH)model in rat was u ed. Changes in myosin isoenzymes, and qualitative and quantitative changes in collagen in the ventricles were examined. Changes in beta-receptors were also examined. Moreover, effects of ACE inhibitor and Ca antagonist on protein metabolisms of RVH were also examined. RESULTS : (1)MIE in the RV as well as in the LV shifted from Vl to V3 during the development of RVH. (2)Although collagen concentration of the ventricles did not alter, types Ill and V collagens in the RV increased. (3)Numbers of beta-receptors decreased not only in the RV, but also in the LV. These changes became much more prominent as RVH became pronounced, resulting in congestive heart failure. (4)Derapril-HCl(ACE inhibitor ; 30 mg/kg/day)and Nilvadipine(Ca antagonist ; 3 mg/kg/day)reduced systolic RV pressure to the same extent and inhibited RVH. The inhibitory effect of ACE inhibitor was more strong than that of Ca antagonist. Both drugs reversed the changes in MIE to the same extent. Although total collagen contents of the RV decreased by treatment with both drugs, ACE inhibitor did not decrease collagen concentration while Ca antagonist decreased collagen concentration. Moreover, ACE inhibitor did not reverse changes in collagen types while Ca antagonist reversed them. CONCLUSIONS : Our results revealed that the heart adapts to pressure overload by changing contractile and noncontractile protein metabolisms quantitatively and qualitatively. However, pronounced changes in these protein metabolisms lead to maladaptation to a pressure overload. Detailed effects of anti-hypertensive drugs on contractile and noncontractile protein metabolisms, but not simple effects of them on cardiac mass, are necessary to evaluate the exact usefulness of anti-hypertensive agents on cardiac hypertrophy in response to a pressure overload. Less

肌球蛋白和胶原蛋白是心脏的主要成分。已经揭示，当心脏接收压力超负荷时，不仅收缩蛋白质而且胶原代谢也定量和定性地改变。然而，心肌肥大时收缩性和非收缩性蛋白质代谢的相对变化尚未同时阐明，其含义仍不清楚。此外，已知与心脏功能密切相关的β受体在心脏肥大的发展过程中发生变化。在这项研究中，我们同时检查了压力超负荷和非压力超负荷心室的上述参数。我们还研究了抗高血压药物对肥厚心脏上述参数的影响，并从收缩性和非收缩性蛋白质代谢的角度分析了这些抗高血压药物的优缺点。材料与方法：野百合碱诱导的右心室肥厚模型。 ...更多信息 采用大鼠肥厚模型，观察了心室肌球蛋白同工酶的变化及胶原的定性和定量变化。还检查了β受体的变化。此外，还观察了ACE抑制剂和Ca ~（2+）拮抗剂对RVH蛋白质代谢的影响。结果：（1）在RVH发生过程中，RV和LV的MIE均由V1向V3移动。（2）虽然心室胶原含量无明显变化，但右心室III型和V型胶原含量增加。（3）不仅右室β受体数量减少，左室β受体数量也减少。随着RVH变得明显，这些变化变得更加突出，导致充血性心力衰竭。（4）Derapril-HCl（ACE抑制剂; 30 mg/kg/天）和Nilvadipine（Ca拮抗剂; 3 mg/kg/天）降低RV收缩压的程度相同，并抑制RVH。ACE抑制剂的抑制作用强于Ca拮抗剂。两种药物在相同程度上逆转了MIE的变化。虽然总胶原含量的RV减少治疗与两种药物，ACE抑制剂并没有减少胶原浓度，而钙拮抗剂减少胶原浓度。此外，ACE抑制剂没有逆转胶原类型的变化，而钙拮抗剂逆转它们。结论：我们的研究结果表明，心脏适应压力超负荷通过改变收缩和非收缩蛋白质代谢的定量和定性。然而，这些蛋白质代谢的显著变化导致对压力过载的适应不良。降压药对收缩性和非收缩性蛋白质代谢的详细影响，而不是它们对心脏质量的简单影响，对于评价降压药对压力超负荷引起的心脏肥大的确切作用是必要的。少

项目成果

Honda, M., Hashimoto, M., Ishikawa, S., Yamada, S., Kuzuo, H., Goto, Y., Ishinaga, Y., Kuzuo, H., Tanaka, K., Kuramochi, T., Morioka, S., Moriyama, K.: "Effects of ACE inhibitor and calcium antagonist on myosin and collagen metabolism in right ventricular

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S.Ishikawa,M.Honda et al: "Biventricular down regulation of adrenergic receptors in monocrotaline treated rats"

S.Ishikawa、M.Honda 等人：“野百合碱治疗大鼠中肾上腺素能受体的双心室下调”

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Shigenori Ishikawa: "Biventricular Remodeling of Myosin and Collagen in Pulmonary Hypertension" J Clin Exp Pharmacol Physiol.

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Honda,M.: "Biochemical and Ultrastructural Remodelings of Collegen in Right Ventricular Hypertrophy Induced by Monocrotaline" Japanese Circualtion Journal.

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