Previously in this chapter, we discussed the effects of stimulation of central and peripheral chemoreceptors on cardiac performance. These effects typically dominate, but it's important to note that oxygen (O2) and carbon dioxide (CO2) also have direct effects on the heart muscle.

Mild hypoxia actually stimulates myocardial performance, while more severe hypoxia depresses performance due to limitations in oxidative metabolism.

An increase in the partial pressure of carbon dioxide (PCO2), leading to a decrease in pH, directly depresses the heart. This is mediated by changes in intracellular pH. An increase in PCO2 reduces intracellular pH, which in turn decreases the amount of calcium (Ca++) released from the sarcoplasmic reticulum in response to excitation. It also reduces the sensitivity of the myofilaments to Ca++. On the other hand, increases in intracellular pH enhance sensitivity to Ca++.

The regulation of the peripheral circulation is controlled both centrally by the nervous system and locally by conditions in the surrounding tissues. The control mechanisms vary in importance across different tissues.

Arterioles play a crucial role in regulating blood flow throughout the body. They offer the highest resistance to the flow of blood pumped by the heart and therefore contribute significantly to maintaining arterial blood pressure. Arteriole walls are mainly composed of smooth muscle fibers that allow the diameter of the vessel lumen to change. Contraction of the smooth muscle causes the endothelial lining to fold inward and close the vessel, while relaxation maximizes the vessel's diameter. It's worth noting that some resistance vessels are closed at any given time and the smooth muscle in these vessels is partially contracted, contributing to vascular tone. If all resistance vessels dilated simultaneously, arterial blood pressure would dramatically decrease.

Vascular smooth muscle is responsible for controlling total peripheral resistance, arterial and venous tone, and the distribution of blood flow throughout the body. The properties of vascular smooth muscle are discussed elsewhere. In the following sections, we will review the intrinsic and extrinsic control of vascular smooth muscle tone and its impact on perfusion of peripheral tissues.

In certain tissues, blood flow is adjusted based on the metabolic activity of the tissue. Additionally, when tissue metabolism is stable, changes in perfusion pressure (arterial blood pressure) lead to changes in vascular resistance, aiming to maintain a consistent blood flow. This autoregulation of blood flow is known as the myogenic mechanism, as shown in the graphical representation. When pressure is abruptly increased or decreased from a control pressure of 100 mm Hg, flow also increases or decreases accordingly. However, even when pressure is maintained at the new level, blood flow gradually returns to the control level within 30 to 60 seconds.
Changes in cardiac performance as a result of stimulation of central and peripheral chemoreceptors have been described previously in this chapter. These effects usually predominate. However, O2 and CO2 do have direct effects on the myocardium.
Hypoxia has a biphasic effect on myocardial performance. Mild hypoxia stimulates performance, but more severe hypoxia depresses performance because oxidative metabolism is limited.
An increase in partial pressure of carbon dioxide (PCO2)— which results in a decrease in pH—has a direct depressant effect on the heart. This effect is mediated by changes in intracellular pH. A reduction in intracellular pH, induced by an increase in PCO2, diminishes the amount of Ca++ released from the sarcoplasmic reticulum in response to excitation. The diminished pH also decreases the sensitivity of the myofilaments to Ca++ . Increases in intracellular pH have the opposite effect; that is, they enhance sensitivity to Ca++ .
Regulation of the Peripheral Circulation
The peripheral circulation is essentially under dual control: centrally through the nervous system and locally by conditions in tissues surrounding the blood vessels. Nervous and humoral regulation of vascular smooth muscle is described in
Fig. 14.7
Table 14.1 ), in which transmitters, hormones and their receptors are discussed. Aspects of local control are discussed in , in which the relative importance of these two control mechanisms is shown to vary in different tissues.
The arterioles are involved in regulating the rate of blood flow throughout the body. These vessels offer the greatest resistance to the flow of blood pumped to the tissues by the heart, and thus these vessels are important in the maintenance of arterial blood pressure. The arteriole walls are composed in large part of smooth muscle fibers that allow the diameter of the vessel lumen to vary (see
Fig.
15.2 ). When this smooth muscle contracts strongly, the endothelial lining folds inward and completely obliterates the vessel lumen. When the smooth muscle is completely relaxed, the vessel lumen is maximally dilated. Some resistance vessels are closed at any given time. In addition, the smooth muscle in these vessels is partially contracted (which accounts for the tone of these vessels). If all the resistance vessels in the body dilated simultaneously, arterial blood pressure would fall precipitously.
Vascular smooth muscle controls total peripheral resistance, arterial and venous tone, and the distribution of blood flow throughout the body. The properties of vascular smooth muscle are discussed in . In the following sections, intrinsic and extrinsic control of vascular smooth muscle tone, and thus perfusion of peripheral tissues, is reviewed.
Intrinsic or Local Control of Peripheral Blood Flow
In certain tissues, blood flow is adjusted to the existing metabolic activity of the tissue. Furthermore, when tissue metabolism is steady, changes in perfusion pressure (arterial blood pressure) evoke changes in vascular resistance that tend to maintain a constant blood flow. This myogenic mechanism, which is illustrated graphically in
Fig. 18.22 , is commonly referred to as autoregulation of blood flow. When pressure is abruptly increased or decreased from a control pressure of 100 mm Hg, flow increases or decreases, respectively. However, even with pressure maintained at its new level, blood flow returns toward the control level within 30 to 60 seconds.