Endothelial cell functions in the hemodynamic responses to stress.
ACE is a function of the endothelial cell that appears vital to integrative homeostatic physiology in stress. The endothelial cell, both in the lung and in systemic tissues, is uniquely situated to detect changes in ambient oxygen tension; thereafter, as exemplified by the effects of altered oxygen tension on ACE, the cell is capable of initiating changes that modulate its functions to reflect the altered physiologic state. Based upon extensive studies of endothelial cells propagated in tissue culture, these altered functions are rapid in onset, rapidly reversible, and quite closely correlated to PO2. Integrity of the endothelial cell membrane is necessary for the modulating changes to occur, and indeed, ACE purified from the cell is insensitive to changes in oxygen tension: it is the cell, not the enzyme, that responds to changes in oxygen tension (FIGURE 5). It is important to emphasize the interdependent nature of the several vasoactive systems. The kallikrein-kinin system, in addition to its putative role in blood pressure regulation, is an intimate component of both the coagulation and fibrinolysis plasma protease cascades. The sympathetic nervous system has multiple points of interdigitation in both the kallikrein-kinin and the renin-angiotensin systems; high levels of epinephrine stimulate renin release and activate both plasma and tissue kallikrein. In turn, both of the vasoactive peptides of these systems, bradykinin and angiotensin II, stimulate epinephrine production from the adrenal medulla. Angiotensin II enhances the potency of norepinephrine released from postganglionic sympathetic nerve endings, increasing alpha-adrenergic tone. In addition, multiple interactions have been described between angiotensin II and bradykinin and the formation of prostaglandins by endothelial cells. Preliminary data indicate that the potency of these peptides in causing prostanoid release is, as might be expected, closely correlated to ACE activity, which itself is a function of ambient PO2. These multiple interactions are diagrammed in FIGURE 9. It is noteworthy that the two fundamental regulators of the circulation, pH and PO2, can be shown to interact at the most basic level with endothelial cell function.
D000531:Altitude; D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D001808:Blood Vessels / Q000503:physiopathology*; D001920:Bradykinin / Q000502:physiology; D002199:Capillary Permeability; D004727:Endothelium / Q000201:enzymology / Q000503:physiopathology*; D006439:Hemodynamics; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000032:analysis; D005082:Physical Exertion; D013312:Stress, Physiological / Q000503:physiopathology*
D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin