REGULATION OF INTRAPULMONARY AIRWAYS AND VESSELS

这项研究的主要目的是改善我们的 血管平滑肌松弛机制的理解 肺。 调节血管的细胞机制的基础知识 肺中的平滑肌张力是新形式的发展所必需的 肺源性心脏病、肺动脉高压和肺动脉高压的血管扩张治疗 持续性胎儿循环综合征 尽管越来越多地使用 降低肺动脉压和肺动脉压的血管扩张剂药物 血管阻力在上述疾病中，如果有的话， 已知这些药物松弛血管平滑肌的机制 肺部肌肉 我们实验室的研究表明， 明显不同类型的试剂：有机硝酸盐和亚硝酸盐， 三尖杉酯碱、β-肾上腺素能激动剂和钙通道阻滞剂 药物，降低肺血管张力时肺血管阻力 已经被一个活跃的过程所增加。 在这一建议中， 肺内动脉螺旋段和螺旋环的实验研究 对这些血管的静脉和生化研究将提高我们的 了解这四类药物对平滑肌的影响 张力和这些药物松弛血管平滑肌的机制 从肺部。 这些实验应该提供更好的理解 环鸟苷酸在平滑肌松弛中作用及改善我们的电流 了解哺乳动物环鸟苷酸的生物学意义 细胞 这项提案的总体统一目标是改善我们的 肺血管扩张机制的知识。

The principal objective of the proposed research is to improve our understanding of relaxation mechanisms in vascular smooth muscle from the lung. Fundamental knowledge of cellular mechanism which regulate vascular smooth muscle tone in the lung is needed for the development of new forms of vasodilator therapy for cor pulmonale, pulnonary hypertension and the persistent fetal circulation syndrome. In spite of the increased use of vasodilaror drugs to reduce pulnonary arterial pressure and pulmonary vascular resistance in the above mentioned disorders, little if anything is known about the mechanisms by which these agents relax vascular smooth muscle from the lung. Studies in our laboratory have shown that four distinctly different types of agents: organic nitrates and nitrites, prostaglandins, beta-adrenergic agonists and calcium channel blocking agents, decrease pulmonary vascular resistance when pulmonary vascular tone has been increased by an active process. In this proposal, relaxation experiments on isolated helical segments and rings of intrapulmonary artery and vein and biochemical studies on these vessels will improve our knowledge of the effects of these four classes of agents on smooth muscle tone and the mechanism by which these agents relax vascular smooth muscle from the lung. These experiments should provide a better understanding of the role of cyclic GMP in smooth muscle relaxation and improve our current understanding of the biological significance of cyclic GMP in mammalian cells. The overall unifying goal of this proposal is to improve our knowledge of vasodilator mechanisms in the lung.