Chapter 19 Introduction to the Regulation of Cardiovascular Function
| Abbreviations | |
|---|---|
| ACh | Acetylcholine |
| ANS | Autonomic nervous system |
| CNS | Central nervous system |
| Epi | Epinephrine |
| NE | Norepinephrine |
| NPY | Neuropeptide Y |
Dysfunction of the cardiovascular system is the principal cause of death and disability in middle-aged and elderly men and women in the industrialized world. In the United States in 2004, there were nearly 1 million deaths from cardiovascular disease, representing approximately 36% of all deaths. In addition, estimates of the prevalence of cardiovascular disease in 2005 indicated that more than 70 million individuals had hypertension, 16 million had coronary heart disease, and more than 5 million had congestive heart failure (Table 19-1). To best understand pharmacological approaches to the management of these disorders, an overview of the regulation of cardiovascular function is warranted.
TABLE 19–1 Prevalence of Cardiovascular Disease in the United States in 2005*
| Hypertension | 73 |
| Coronary heart disease | 16 |
| Myocardial infarction | 8.1 |
| Angina pectoris | 9.1 |
| Stroke | 5.8 |
| Congestive heart failure | 5.3 |
* Data from the American Heart Association; numbers represent millions of persons.
The ANS innervates the heart, blood vessels, kidney, and adrenal medulla and has the potential to modify cardiovascular function in a number of different ways (see Chapter 9).
The overall coordination and integration of organismal cardiovascular function is accomplished primarily by the ANS. Through its sympathetic and parasympathetic limbs, the ANS has powerful effects on both cardiac performance and blood vessel caliber (see Chapter 9).
The sympathetic and parasympathetic nerves innervating cardiovascular end organs are tonically active, which means that activity can be modulated by either increasing or decreasing the firing rate of these nerves. Effects of autonomic nerve activity on the mechanisms that control blood pressure are summarized in Figure 19-1. Parasympathetic effects are mediated by acetylcholine (ACh) released from postganglionic parasympathetic nerve endings, whereas sympathetic effects are mediated by norepinephrine (NE) released from postganglionic sympathetic nerve endings. Although there is no circulating ACh because of high cholinesterase activity in both tissue and blood, NE released from postganglionic sympathetic nerve endings escapes into the circulation because its degradation or reuptake is incomplete. This source of NE, in concert with the epinephrine (Epi) and NE released into the blood from the adrenal medulla, influence cardiovascular function as circulating neurohormones (see Chapter 9).
Ventricular contractile force is little influenced by parasympathetic activity but can be greatly increased by sympathetic activity, including the actions of circulating Epi and NE. Increased sympathetic activity reduces vascular caliber by contracting vascular smooth muscle. Although there are parasympathetic influences on a few vascular beds, their contribution to overall vascular resistance is insignificant. Constriction of veins in response to sympathetic activity reduces venous capacitance, thereby increasing venous return to the heart, which augments atrial and ventricular filling, resulting in increased cardiac output. Sympathetically mediated constriction of arterioles can reduce cardiac output by increasing the resistance against which the heart must pump blood. In addition, elevated sympathetic activity to the kidney increases renin release and subsequent angiotensin II formation and causes causing Na+ and H2O retention. All of these effects act in concert to elevate arterial blood pressure. Conversely, a reduction of sympathetic activity reduces blood pressure by removing the sympathetic stimulus. The receptors and signaling pathways involved are discussed in Chapter 9.
