Porth's Essentials of Pathophysiology, 4e

399

Control of Cardiovascular Function

C h a p t e r 1 7

nitric oxide production and vessel relaxation. Nitric oxide also inhibits platelet aggregation and secretion of platelet contents, many of which cause vasoconstric- tion. Nitroglycerin, a drug used in treatment of angina, produces its effects by releasing nitric oxide in vascular smooth muscle of the target tissues. The endothelium also produces a number of vaso- constrictor substances, including angiotensin II , vaso- constrictor prostaglandins, and a family of peptides called endothelins . There are at least three endothelins. Endothelin-1 is the most potent endogenous vasocon- strictor known. Humoral Control of Blood Flow Humoral control of blood flow involves the effect of vasodilator and vasoconstrictor substances in the blood. Some of these substances are formed by special glands and transported in the blood throughout the entire cir- culation. Others are formed in local tissues and aid in the local control of blood flow. Among the most impor- tant of the humoral factors are norepinephrine and epinephrine, angiotensin II, histamine, serotonin, bra- dykinin, and the prostaglandins. Norepinephrine and Epinephrine. Norepinephrine is an especially powerful vasoconstrictor hormone; epi- nephrine is less so and in some tissues (e.g., skeletal muscle) even causes mild vasodilation. Stimulation of the sympathetic nervous system during stress or exercise causes local constriction of veins and arterioles due to the release of norepinephrine from sympathetic nerve endings. In addition, sympathetic stimulation causes the adrenal medullae to secrete both norepinephrine and epinephrine into the blood. These hormones then circu- late in the blood, causing direct sympathetic stimulation of blood vessels in all parts of the body. Angiotensin II. Angiotensin II, another powerful vasoconstrictor, is produced as a part of the renin-angiotensin-aldosterone system. It normally acts on many arterioles at the same time to increase the periph- eral vascular resistance, thereby increasing the arterial blood pressure (discussed in Chapter 18). Histamine. Histamine has a powerful vasodilator effect on arterioles and has the ability to increase cap- illary permeability, allowing leakage of both fluid and plasma proteins into the tissues. Histamine is largely derived from mast cells in injured tissues and basophils in the blood. In certain tissues, such as skeletal muscle, the activity of the mast cells is mediated by the sym- pathetic nervous system; when sympathetic control is withdrawn, the mast cells release histamine. Serotonin. Serotonin, which is liberated from aggregat- ing platelets during the clotting process, causes vasocon- striction and plays a major role in control of bleeding. Serotonin is found in brain and lung tissues, and there is some speculation that it may be involved in the vascular spasm associated with some allergic pulmonary reac- tions and migraine headaches.

Bradykinin. The kinins (i.e., kallidins and bradykinin) are small polypeptides that are liberated from the glob- ulin kininogen, which is present in body fluids. They cause powerful vasodilation when formed in the blood and tissue fluids of organs. Bradykinin causes intense dilation of arterioles, increased capillary permeability, and constriction of venules. It is thought that the kinins play special roles in regulating blood flow and capillary leakage in inflamed tissues. It is also believed that brady- kinin plays a major role in regulating blood flow in the skin as well in the salivary and gastrointestinal glands. Prostaglandins. Prostaglandins are synthesized from constituents of the cell membrane (i.e., the long-chain fatty acid arachidonic acid ). Tissue injury incites the release of arachidonic acid from the cell membrane, which initiates prostaglandin synthesis (see Chapter 3, Fig. 3-4). There are several prostaglandins (e.g., E2, F2, D2), which are subgrouped according to their solubility; some produce vasoconstriction and some produce vaso- dilation. As a general rule, those in the E group are vaso- dilators and those in the F group are vasoconstrictors. The corticosteroid hormones produce an anti-inflam- matory response by blocking the release of arachidonic acid, thereby preventing prostaglandin synthesis. Collateral Circulation Collateral circulation is a mechanism for the long-term regulation of local blood flow. In the heart and other vital structures, anastomotic channels exist between some of the smaller arteries. These channels permit per- fusion of an area by more than one artery. When one artery becomes occluded, these anastomotic channels increase in size, allowing blood from a patent artery to perfuse the area supplied by the occluded vessel. For example, persons with extensive obstruction of a coro- nary blood vessel may rely on collateral circulation to meet the oxygen needs of the myocardial tissue normally supplied by that vessel. As with other long-term com- pensatory mechanisms, the recruitment of collateral cir- culation is most efficient when the obstruction to flow is gradual, rather than sudden. Neural Control of Blood Flow The neural control of the circulation occurs primar- ily through the sympathetic and parasympathetic divi- sions of the autonomic nervous system (ANS). The ANS contributes to the control of cardiovascular func- tion through modulation of cardiac function (i.e., heart rate and cardiac contractility) and peripheral vascular resistance. The neural control centers for the integration and modulation of cardiac function and blood pressure are located bilaterally in the medulla oblongata of the brain. The medullary cardiovascular neurons are grouped into three distinct pools that lead to sympathetic innerva- tion of the heart and blood vessels and parasympathetic innervation of the heart. The first two, which control