INTERACTION OF HEMOGLOBIN/EDRF IN CARDIOVASCULAR CONTROL

血红蛋白将被用作血液替代品，如果心血管疾病 这些溶液的作用不会引起显著的毒性。的 本申请的目的是确定 牛聚合血红蛋白。由于血红蛋白结合氮 我们的建议的具体目标是确定血红蛋白 通过NO干扰循环的生理控制。 给药后循环中发生的明显变化 含有血红蛋白的溶液是动脉压的增加， 血管阻力了解负责 这是电阻增加和反射调制的部位 机制将是这项建议的第一个具体目标。第二 具体目标将集中于含血红蛋白溶液的能力 这主要取决于四聚体的能力， 血红蛋白扩散之间的内皮细胞和底层 平滑肌细胞我们认为血红蛋白的聚合物不会 由于尺寸大，扩散，不会增加动脉压。 毕竟，红细胞中所含的血红蛋白并不 间质EDRF。我们建议的第三个具体目标是， 含有血红蛋白的溶液也改变了氧气的使用方式 被周围组织破坏这是基于这样的观察， 使用取代的精氨酸分子显著抑制NO形成 改变心脏和骨骼肌的氧提取和消耗。 第四个具体目标是确定重复施用 含有血红蛋白的溶液改变了血液中NO的产生 血管和生物化学和分子机制负责这一点。 我们的研究将在长期使用器械的犬和组织中进行 来自相同的动物。我们相信，这将使我们的推断， 结果对人类心血管控制和对 血红蛋白改变的心血管控制机制 含有溶液。

Hemoglobins will be used as a blood substitute if the cardiovascular actions of these solutions do not cause significant toxicity. The objective of this application is to determine the physiologic actions of bovine polymerized hemoglobins in dogs. Since hemoglobin binds nitric oxide the specific aims of our proposal are to determine how hemoglobin interferes with the physiologic control of the circulation by NO. The most obvious change which occurs in the circulation after administration of hemoglobin containing solutions is an increase in arterial pressure and vascular resistance. An understanding of the mechanisms responsible for this, the site of the increase in resistance and modulation by reflex mechanisms will be the first specific aim of this proposal. The second specific aim will focus on the ability of hemoglobin containing solutions to scavenge NO. This depends primarily on the ability of tetrameric hemoglobin to diffuse between the endothelial cell and the underlying smooth muscle cell. We propose that polymers of hemoglobin will not diffuse due to the large size and will not increase arterial pressure. After all, hemoglobin contained in red cells does not scavenge interstitial EDRF. The third specific aim of our proposal is that hemoglobin containing solutions also alter the way in which oxygen is used by the peripheral tissues. This is based on the observation that inhibition of NO formation using substituted arginine molecules markedly alters oxygen extraction and consumption by the heart and skeletal muscle. The fourth specific aim is to determine if the repeated administration of hemoglobin containing solutions alters the production of NO by blood vessels and the biochemical and molecular mechanism responsible for this. Our studies will be conducted in chronically instrumented dogs and tissues from the same animals. This, we believe will allow extrapolation of our results to cardiovascular control in man and to a understanding of the mechanisms of cardiovascular control which are modified by hemoglobin containing solutions.