Robert D. Furchgott’s Contribution To Physiology And The Discovery Of Nitric Oxide As A Cardiovascular Signaling Molecule

1988 words - 8 pages

Robert F. Furchgott’s Prior Work in Pharmacology and Physiology
Robert F. Furchgott was awarded a Bachelor of Science from the University of North Carolina in 1937 and a PhD in biochemistry from Northwestern University in 19401,2. During this PhD, he initially examined the physical and chemical changes egg albumin denaturation produced, but after attending a symposium in 1938 he decided to study the effects of unbuffered isotonic solution on mammalian erythrocytes6. He discovered a serum albumin that he coined “anti-sphering factor” that could not be separated from erythrocytes by traditional methods5.
After receiving his PhD, he worked with Dr. Ephraim Shorr, first studying phosphate exchange and regeneration in canine ventricular muscle and then studying circulatory shock, including the effects of hemorrhagic hypoxia on tissue energy and the process of “irreversible” shock whereby increased blood volume is not able to raise pressure due to controlled hemmorhage6. He and his colleagues found two substances produced during circulatory shock, vasoexcitatory material (VEM), produced in the kidney, which increased arteriole precapillary sphincter sensitivity to epinephrine during reversible circulatory shock, and vasodepressor material (VDM), produced in the liver, which decreased sensitivity during irreversible shock6. These findings were published in Science in 19456.
Furchgott accepted an assistant professorship in pharmacology at Washington University in 19496. By 1951 he started using rabbit aortic strip to study drug-receptor interactions, and in 1953 he published a paper detailing the reactions of rabbit aorta strips to epinephrine, isoprenaline, sodium nitrite, and other drugs such as acetylcholine (ACh)6. He noticed (as other researchers had) that in vitro ACh, a well-known in vivo vasodilator, produced contraction in the aorta strips he studied; the cause of this would later be evident6. In 1954 Furchgott published a paper outlining aortic strip receptor differentiation using dibenamine, and in 1955, a review on the pharmacology of smooth muscle that developed receptor theory as the main way drugs interact and produce effects in tissues6. The review also explored the concept of photorelaxation in rabbit aorta strips2,6. Furchgott and colleagues also investigated varying concentrations of creatinine phosphate, ATP, ADP, and AMP as sources of experimental failure (diminishing contraction over time) in in vitro tissues and found no correlation.
Furchgott accepted the position of chairman at the new pharmacology department at State University of New York College of Medicine in 19566. Furchgott and colleagues showed that myogenic contractility was associated with an increase in the exchange rate of calcium from an intracellular pool and were able to link the contractile effects of noradrenaline, strophathin-K, acetylcholine and adenosine to this calcium store6. Furthermore, he was able to show that a decrease in...

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