Study of Right Ventricular Hypertrophy in Experimental Pulmonary Hypertension

目的：肌球蛋白和胶原蛋白是心脏的主要成分。研究表明，当心脏承受压力过载时，不仅收缩蛋白，胶原蛋白的代谢也会发生定量和定性的变化。然而，心肌肥厚中收缩性和非收缩性蛋白代谢的相对变化尚未同时明确，其意义尚不清楚。此外，已知与心功能密切相关的β受体在心脏肥厚的发展过程中发生变化。在这项研究中，我们同时检测了压力过载和非压力过载心室的上述参数。我们还观察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：建立大鼠右心室肥厚（RVH）模型，检测心室肌球蛋白同工酶变化及胶原质定量变化。β受体的变化也被检测。此外，我们还研究了ACE抑制剂和Ca拮抗剂对RVH蛋白代谢的影响。结果：(1)在RVH的发展过程中，右心室和左室的MIE由Vl向V3转移。(2)虽然心室胶原浓度没有变化，但左心室的i型和V型胶原增加。(3) β受体数量不仅在右室减少，而且在左室也减少。当RVH变得明显时，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/day）和Nilvadipine（Ca拮抗剂，3 mg/kg/day）降低RV收缩压的程度相同，抑制RVH。ACE抑制剂的抑制作用强于钙拮抗剂。两种药物在相同程度上逆转了MIE的变化。虽然两种药物均降低了RV的总胶原含量，但ACE抑制剂没有降低胶原浓度，而Ca拮抗剂降低了胶原浓度。此外，ACE抑制剂不能逆转胶原类型的变化，而Ca拮抗剂可以逆转胶原类型的变化。结论：我们的研究结果表明，心脏通过定量和定性地改变收缩性和非收缩性蛋白质代谢来适应压力过载。然而，这些蛋白质代谢的显著变化导致对压力过载的不适应。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，对于评估降压药在压力过载时对心脏肥厚的确切作用是必要的。少

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