Relaxing And Contracting Factors: Biological And Clinical Research (the Endothelium)

It is an exciting task to be the editor of the first monograph covering a new area of the biomedical sciences. Since the first report in 1980 by Robert Furchgott and colleagues (see Chapter 1) of the evidence of endothelium-dependent relaxation in isolated arteries, there are ever­ increasing numbers of vascular physiologists and pharmacologists who are scraping away the endothelium to look into its role in cardiovascular con­ trol. And the more one looks, the more one discovers. Not only is the list of substances that can induce endothelium-dependent relaxations im­ pressively long, but these intriguing cells can also secrete vasoconstrictor substances. The ability of the endothelium to modulate the degree of con­ traction of the underlying smooth muscle is an ancestral property of the blood vessel wall, illustrating the logic of nature, since the endothelial cells are located in the best possible strategic location to continuously monitor the properties (chemical or physical) of the blood. And more and more data emerge suggesting that in several cardiovascular diseases per­ turbations in endothelium-dependent responses are one of the early signs of the abnormal process. Thus, the importance of endothelium-dependent responses, triggered by the intellectual curiosity of one of the pioneers of vascular physiology and pharmacology, is now recognized not only by basic scientists, but also by all concerned with the cardiovascular diseases. The purpose of this monograph is to provide them with a reference work, so that they know where to start. Front Matter....Pages i-xxv Endothelium-Dependent Relaxation in Systemic Arteries....Pages 1-26 Endothelium-Dependent Contractions in Veins and Arteries....Pages 27-39 The Nature of Endothelium-Derived Relaxing Factor....Pages 41-64 Metabolism of Arachidonic Acid and Release of Endothelium-Derived Relaxing Factors....Pages 65-89 Modulation of the Release and Biological Activity of Endothelium-Derived Relaxing Factor by Oxygen-Derived Free Radicals....Pages 91-105 Endothelial Cells in Culture and Production of Endothelium-Derived Relaxing Factor....Pages 107-135 Endothelial Cells in Culture and Production of Endothelium-Derived Constricting Factors....Pages 137-158 Basal Release of Endothelium-Derived Relaxing Factor....Pages 159-178 Calcium Transport Mechanisms in Endothelial Cells Regulating the Synthesis and Release of Endothelium-Derived Relaxing Factor....Pages 179-188 Release of Endothelium-Derived Relaxing Factor(s) by Physicochemical Stimuli....Pages 189-217 Role of Cyclic GMP in Endothelium-Dependent Relaxation of Vascular Smooth Muscle....Pages 219-239 Modulation by the Endothelium of Agonist-Induced Contractions of Vascular Smooth Muscle....Pages 241-265 Endothelium-Derived Relaxing Factor Relaxes Vascular Smooth Muscle by Cyclic GMP-Mediated Effects on Calcium Movements....Pages 267-283 Heterogeneity in Endothelium-Dependent Relaxations Acute, Chronic, and Evolutionary Modulations....Pages 285-307 Endothelium-Dependent Regulation of Resting Levels of Cyclic GMP and Cyclic AMP and Tension in Pulmonary Arteries and Veins....Pages 309-332 Endothelium-Dependent Reponses of Cerebral Arteries....Pages 333-345 Endothelium, Blood Flow, and Vascular Responses in Large Coronary and Iliac Arteries of the Conscious Dog....Pages 347-360 Endothelium-Dependent Responses in Large Arteries and in the Microcirculation....Pages 361-387 Endothelium-Dependent Responses in the Peripheral Microcirculation....Pages 389-416 Endothelium-Dependent Vasodilatation in the Cerebral Microcirculation....Pages 417-424 Platelets and Endothelium-Dependent Responses....Pages 425-449 Endothelium-Dependent Responses and the Release of Endothelium-Derived Relaxing Factor in Atherosclerotic Blood Vessels....Pages 451-472 Endothelium-Dependent Relaxations in Hypertensive Blood Vessels....Pages 473-494 Mechanisms of Altered Endothelium-Dependent Responses in Hypertensive Blood Vessels....Pages 495-509 Endothelium-Dependent Responses in Human Arteries....Pages 511-528 Back Matter....Pages 529-543