This chapter deals with the autonomic nervous system (ANS). This regulates the operation of the internal organs and supports the activity of the body as a whole. The autonomic nervous system is not a separate nervous system but is the efferent pathway that links those areas within the brain concerned with the regulation of the internal environment to specific effectors such as blood vessels, the heart, and the gut. The chapter points out that the ANS does not pass directly to the effector organs, but rather they synapse in autonomic ganglia, which are located outside the CNS. The chapter looks at fibres. These project from the CNS to the autonomic ganglia. The latter are called preganglionic fibres, and those that connect the ganglia to their target organs are called postganglionic fibres. The sensory nerves of the internal organs are known as visceral afferents.
Chapter
The autonomic nervous system
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Thromboxane antagonists
This chapter defines thromboxane A2 as a naturally occurring substance that has the undesirable effects of bronchoconstriction, aggregation of the blood platelets, and constriction of the blood vessels whenever it is released in the body. The inhibition of the effects of thromboxane A2 could lead to a potential treatment for circulatory or respiratory disorders. The chapter discusses a series of thromboxane antagonists that have been developed in ICI. These have similar structures to thromboxane A2 and are therefore able to block the relevant receptor site in the body. The chapter highlights that the synthetic challenge for a compound to be viable as a pharmaceutical agent is achieving stereochemical control using methods that can be operated on a larger scale. The chapter covers different compounds that were synthesized in small quantities using a route that enabled the synthesis of many analogues for biological evaluation.
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Atherosclerosis and ischaemic heart disease
This chapter focuses on atherosclerosis and ischaemic heart disease. The chapter shows that the blockage of blood vessels reduces the supply of oxygenated blood to areas of the heart muscle, which then causes myocardial ischaemia or ischaemic heart disease. The chapter then examines the underlying disease of the coronary arteries caused by atherosclerosis. Lifestyle changes, including regular exercise, reduction in alcohol intake, and the cessation of smoking offer great benefits in the prevention of ischaemic heart disease. The chapter explains how lipid-lowering drugs prevent atherosclerosis before detailing the types of angina and myocardial infarction caused by a thrombotic event in a diseased coronary artery leading to a sudden decrease in blood flow.
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Angiogenesis
This chapter focuses on the process of forming new blood vessels from pre-existing ones by the growth and migration of endothelial cells — angiogenesis. It argues that this process is common during embryogenesis, although it rarely occurs in the adult. The chapter then shows why angiogenesis is essential for most tumors with respect to cancer. It explains the angiogenic switch and the mechanisms of angiogenic sprouting. Sprouting of pre-existing vessels requires major reorganization involving destabilization of the mature vessel, proliferation and migration of endothelial cells, and maturation. It is regulated by the interaction of soluble mediators and their cognate receptors. The chapter then presents the other means of tumor neovascularization and elaborates on anti-angiogenic therapy. It then looks at vascular targeting by vascular disrupting agents.
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Cardiovascular systems
This chapter discusses the cardiovascular systems of animals. Most invertebrates have an open circulatory system, although decapod crustaceans and some species of non-cephalopod molluscs have an incompletely closed system. Vertebrates have a closed circulatory system: all blood vessels are lined with endothelium. In water-breathing invertebrates, the ventricle propels the blood around the body and then through the gills for gas-exchange. The chapter then looks at the structure and function of blood vessels. In vertebrates, blood vessels consist of three layers: tunica intima, tunica media, and tunica externa. The rate of flow of a fluid through a long straight rigid tube is described by Poiseuille's equation. The major factor affecting the resistance to blood flow is the radius of a blood vessel.
