Allan M. Le fer Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107 David J. Le fer Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland 21224 KEY WORDS: nitric oxide, endothelial dysfunction, adhesion molecules, ischemia-reperfuÂ sion, neutrophils BASIC PHYSIOLOGY OF HUMORAL AGENTS OF ENDOTHELIAL ORIGIN During the past years, great strides have been made in elucidating the regulatory role of the endothelium in vascular dynamics. The endothelium was previously thought of only as a permeability barrier to ions and organic molecules, and as a regional site of metabolic effects, particularly in the pUlmonary microvasculature (i.e. converting angiotensin I to angiotensin II and removing prostaglandins from the circulation) (1). Although these effects are of considerable significance, they did not foretell the far-reaching role of the entire vascular endothelium as an important organ in regulating vascular tone. Cytoprotective Agents Produced by the Endothelium In 1976, Vane, Moncada, and colleagues (2) discovered PGh (prostacyclin), a unique eicosanoid produced by the endothelium. PGh exerts a remarkable constellation of actions, including vasodilation of most vasculatures, inhi- 0362-1642/93/0415-0071$02.00 LEFER & LEFER bition of platelet aggregation, prevention of polymorphonuclear (PMN) leukocyte adherence, and stabilization of membranes (3-5). Prostacyclin has
Annual Review of Pharmacology and Toxicology – Annual Reviews
Published: Apr 1, 1993
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