Although the baroreceptor reflex is the primary moment-to-moment controller of aortic pressure, other
0 50 100 150 200 250 Mean Arterial Pressure (mm Hg)
FIGURE 6 Variations in mean arterial pressure over a 24-hr period in a normal dog before and several weeks after baroreceptor denervation. (Modified from Guyton AC, Hall JE. Textbook of medical physiology, 9th ed. Philadelphia: WB Saunders, 1996.)
mechanisms exist that come into play under periods of extreme cardiovascular stress. These are discussed in the following subsections.
More severe reductions in mean arterial pressure (i.e., when MAP falls below 80 mm Hg) can also be detected by chemoreceptors located in the carotid and aortic bodies. These structures are located near the bifurcation of the common carotid arteries and along the aortic arch. They receive blood via a small nutrient artery and have an extremely high rate of oxygen consumption for their size. Each body contains cells that are sensitive to levels of oxygen, carbon dioxide, and hydrogen ion. Although much of their sensory input goes to the respiratory control centers, some of it goes to the vasomotor center as well. A decrease in MAP causes blood flow to these bodies to fall with a corresponding reduction in oxygen delivery (hypoxia) and an accumulation of CO2 and H+. Information regarding these changes in the chemical environment within the carotid and aortic bodies is transmitted via the carotid sinus and vagus nerves to the vasomotor center. The excited vasomotor center then generates the same responses that it would issue for a fall in carotid sinus pressure, with a resultant rise in arterial pressure. The chemoreceptors are thought to be more intimately involved in detecting changes in blood oxygenation than blood pressure. Hence, only when MAP is drastically reduced do the chemoreceptors reinforce the carotid baroreceptors' efforts to stimulate the vasomotor center to restore the blood pressure.
If MAP is reduced to 60 mm Hg or less, blood flow to the brain becomes significantly impaired. When flow to the brain is reduced below an adequate level, ischemia results. In cerebral ischemia, tissue levels of CO2 and hydrogen ion increase. Chemosensitive cells within the vasomotor center respond directly by sending efferent commands that strongly stimulate both the vagal and sympathetic nerves. Blood flow to virtually all other tissues including the kidneys is reduced in a last ditch attempt to maintain the required flow to the brain and heart. What is peculiar about the cerebral ischemic response is that simultaneous stimulation of both the vagus and the sympathetic nerves results in an increase in myocardial contractility but a net slowing of the heart rate, because the vagus has the stronger influence at the sinoatrial node. Thus, the cerebral ischemic response is characterized by a profound bradycardia.
It is extremely important to recognize that reduced blood flow to the brain may occur for reasons other than a reduced MAP. If cerebrospinal fluid pressure begins to increase, the vessels in the brain will be compressed and cerebral blood flow will fall. A common cause of increased cerebrospinal pressure is bleeding within the skull. In an attempt to restore blood flow to the brain after a cerebral hemorrhage, blood pressure may exceed 250 mm Hg. The pressor response induced by an increase in intracranial pressure is referred to as the Cushing reaction. Although the Cushing reaction may temporarily restore cerebral flow, it can also cause further hemorrhage. Thus, a positive feedback situation can occur in which death rapidly ensues unless the intracranial pressure is relieved.
Four hormonal mechanisms are clearly identified as important in blood pressure control: (1) epinephrine and norepinephrine from the adrenal medulla, (2) vasopressin released from the hypothalamus, (3) the renin-angiotensin system, and (4) atrial natriuretic peptide released in the atria.
The adrenal medulla is a functional extension of the sympathetic nervous system. Activation of the pregan-glionic fibers to the adrenal medulla triggers the release of both epinephrine and norepinephrine directly into the circulation. Norepinephrine is primarily an a-agonist, whereas epinephrine is almost equally divided between a and p effects. Activation of the adrenal medulla usually occurs in concert with activation of the sympathetic nerves to the cardiovascular effectors, and the circulating catecholamines extend and augment their action. The vasoconstrictor effects of circulating catechol-amines persist for only 2-3 min, which is the time required to degrade the adrenergic transmitters. Certain vessels not innervated by adrenergic neurons, such as the metarterioles, can be constricted via this hormonal pathway.
In the section on atrial baroreceptors, it was noted that atrial stretch and increased atrial pressure reduce the hypothalamically controlled secretion of antidiuretic hormone from the posterior pituitary gland. Antidiure-tic hormone functions in both the acute and chronic regulation of blood pressure. As the name implies, the antidiuretic action of the hormone plays an important role in regulating the production of urine by the kidney. Although the hormone can contribute to the pressor responses observed with hemorrhage, it is not thought to be involved in moment-to-moment blood pressure control. Antidiuretic hormone is more often released in response to osmoreceptors in the hypothalamus, which signal that extracellular fluid is becoming hypertonic.
Another important consequence ofincreased filling of the right atrium and the resultant increase in right atrial pressure is the release of atrial natriuretic peptide (ANP) from the myocytes that bear this increased mechanical load. ANP acts on the peripheral vasculature and kidneys in a manner that favors a reduction in arterial blood pressure. The smooth muscle surrounding arterioles relax when exposed to ANP, resulting in a reduction in vascular resistance. ANP also diminishes the barrier function of endothelial cells lining capillaries and post-capillary venules, which favors a redistribution of plasma volume to the extravascular space. Natriuresis, diuresis, and a reduction in renin release are important responses of the kidney to ANP. The combined actions of ANP to cause vasodilation and reduce plasma volume account for the tendency of elevated plasma ANP levels to exert a hypotensive effect. ANP is metabolized by neutral endopeptidases (NEP) that are found in blood, the kidneys, lungs, the central nervous system, and other tissues. Because drugs that inhibit NEP increase plasma ANP levels several times normal and for several hours, NEP inhibitors are gaining recognition as potential therapeutic agents for the management of patients with chronic arterial hypertension.
The kidney functions as an endocrine organ as well as a blood purifier. When renal arterial pressure decreases, the juxtaglomerular cells within the wall of the afferent arterioles secrete renin. Renin secretion can also be stimulated from these cells by activation of their sympathetic innervation. Renin is an enzyme that converts plasma angiotensinogen into angiotensin I. As blood passes through the lungs, angiotensin I is converted into angiotensin II by a converting enzyme produced by the pulmonary endothelial cells. Angioten-sin II is one of the most potent vasoconstrictors known. On a weight basis, it is four to eight times more active than norepinephrine. Angiotensin II increases total peripheral resistance and elicits an intense venoconstric-tion. The renin-angiotensin system represents a mechanism for regulating renal blood flow at the expense of mean arterial pressure. For example, if blood flow to the left kidney is compromised as a consequence of atherosclerotic narrowing of the left renal artery, the kidney will interpret that flow reduction as a low blood pressure and therefore secrete renin in an effort to elevate blood pressure. In restoring the pressure downstream from the atherosclerotic stenosis back to a normal level, the previously underperfused kidney will elevate MAP to an abnormally high level. This condition, which exemplifies the potential impact of the renin-angiotensin system in regulating blood pressure, is called renovascular hypertension and can often be cured by simply bypassing the narrowed artery with a grafted vessel.
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