Vasoactive substances

Substances released from many cells and tissues in the body, including the endothelium lining blood vessels, endocrine glands, and myocytes in the heart, may affect vascular smooth muscle tone. These substances may stimulate this muscle to cause vasoconstriction or inhibit it to cause vasodilation. As expected, vasoconstriction will increase TPR (and therefore MAP) and vasodilation will decrease TPR (and therefore MAP). 

Vasoconstrictors. Many substances produced in the human body cause vasoconstriction under physiological and pathophysiological conditions. Vasoconstrictors of particular importance include  

The major circulating hormones that influence vascular smooth muscle tone are the catecholamines epinephrine and norepinephrine. These hormones are released from the adrenal medulla in response to sympathetic nervous stimulation. In humans, 80% of catecholamine secretion is epinephrine and 20% is norepinephrine. Stimulation of cy-adrenergic receptors causes vasoconstriction. The selective a,-adrenergic receptor antagonist, prazosin, is effective in management of hypertension because it causes arterial and venous smooth muscle to relax. 

Angiotensin II causes vasoconstriction by direct stimulation of ATj receptors on the vascular smooth muscle. It also enhances release of the neurotransmitter norepinephrine from the sympathetic nerve fibers present in the blood vessels. The vasopressor effects of Ag II may be inhibited pharmacologically in order to decrease TPR and treat hypertension. An important class of orally active drugs is the ACE inhibitors, including captopril and enalopril, which prevent formation of Ag II. More recently, angiotensin receptor antagonists have been developed that act at the vascular smooth muscle. These drugs, which include losartin and valsartan, are also orally active. 

Vasopressin (antidiuretic hormone) is a peptide synthesized in the hypothalamus and secreted from the neurohypophysis of the pituitary gland. This substance plays an important role in the long-term regulation of blood pressure through its action on the kidney to increase reabsorption of water. The major stimulus for release of vasopressin is an increase in plasma osmolarity. The resulting reabsorption of water dilutes the plasma toward its normal value of 290 mOsM. This activity is discussed in more detail in Chapter 10 (the endocrine system) and Chapter 19 (the renal system). 

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C3a and C5a are released into the fluid surroundings where they serve as potent anaphylotoxins in that they cause vasoactive substances such as histamines to be released from mast cells and basophils. C5a is also strongly chemotactic for neutrophils. 

Elevated peripheral arterial resistance is a hallmark of primary hypertension. The increase in peripheral resistance typically observed may be due to a reduction in the arterial lumen size as a result of vascular remodeling. This remodeling, or change in vascular tone, may be modulated by various endothelium-derived vasoactive substances, growth factors, and cytokines. This increase in arterial stiffness or reduced compliance results in the observed increase in systolic blood pressure.9... 

The endothelium has many diverse functions that enable it to participate in in-flammatoiy reactions (H27). These include modulation of vascular tone, and hence control of local blood flow changes in structure that allow leakage of fluids and plasma proteins into extravascular tissues local accumulation and subsequent extravasation into tissues of leukocytes and synthesis of surface molecules and soluble factors involved in leukocyte activation (B43). The endothelial cells themselves can modulate vascular tone by the release of vasoactive substances such as prostacyclin, nitric oxide (NO), ET. Endothelium-derived vasoactive substances... 

B32. Boldt, J Menges, T., Kuhn, D., Diridis, C., and Hempelman, G Alterations in circulating vasoactive substances in the critically ill—a comparison between survivors and nonsurvivors. Intensive Care Med. 21,218-225 (1995). 

Vascular hyper-readtvity Hormones Vasoactive substances... 

Another vasoactive substance produced by the endothelium is thromboxane A2 (TxA2). Normally, small amounts of TxA2 are released continuously however, increased synthesis appears to be associated with some cardiac diseases. Synthesized from arachidonic acid, a plasma membrane phospholipid, TxA2 is a potent vasoconstrictor. Furthermore, this substance stimulates platelet aggregation, suggesting that it plays a role in thrombotic events such as myocardial infarction (heart attack). Nonsteroidal anti-inflammatory drugs such as aspirin and ibuprofen block formation of TxA2 and reduce formation of blood clots. 

The mechanisms whereby mast cells enhance host protection to H. polygyms and T. spiralis (and whether these are related to the leak-lesion hypothesis) have not yet been fully defined. Certainly, mast cells contribute to intestinal inflammation during infection through the secretion of a range of cytokines (Gordon et al., 1990) and vasoactive substances (see above). In addition, the release of mast cell proteases are known to increase enterocyte permeability to macromolecules in the rat intestine (Scudamore et al., 1995) and regulate epithelial cell functions at other mucosal sites (Cairns and Walls, 1996). 

The answers are 25-e, 26-b, 27-a. (Hardmanr pp 67—68. Katzung, pp 30, 134.) Anaphylaxis refers to an acute hypersensitivity reaction that appears to be mediated primarily by immunoglobulin E (IgE). Specific antigens can interact with these antibodies and cause sensitized mast cells to release vasoactive substances, such as histamine. Anaphylaxis to penicillin is one of the best-known examples the drug of choice to relieve the symptoms is epinephrine. 

Vasoactive substances (histamine, kinins, prostaglandins) are released at sites of inflammation, increasing blood flow and vascular permeability. This causes edema, warmth, erythema, and pain and makes it easier for granulocytes to pass from blood vessels to sites of inflammation. 

A response to a substance to which an individual has been previously sensitized via the formation of a specific IgE antibody. It is characterized by the release of vasoactive substances and the presence of systemic symptoms. 

Veien and Menne (1990) have suggested that vasoactive substances found in food can enhance nickel sensitivity reactions. Foods that they suggested that nickel-sensitive people should avoid include beer, wine (especially red wine), herring, mackerel, tuna, tomatoes, onions, carrots, apples, and citrus fruits. The vasoactive substances may increase the amount of nickel that is able to reach the skin. 

The Renin-Angiotensin-Aldosterone System and Other Vasoactive Substances 206... 

Endothelial cells produce vasoactive substances, which modulate the permeability of vessel walls accordingly, shear stresses may indirectly affect this wall parameter by influencing the secretory activity of endothelial cells. 

Physiologically, in both normal and hypertensive individuals, blood pressure is maintained by moment-to-moment regulation of cardiac output and peripheral vascular resistance, exerted at three anatomic sites (Figure 11-1) arterioles, postcapillary venules (capacitance vessels), and heart. A fourth anatomic control site, the kidney, contributes to maintenance of blood pressure by regulating the volume of intravascular fluid. Baroreflexes, mediated by autonomic nerves, act in combination with humoral mechanisms, including the renin-angiotensin-aldosterone system, to coordinate function at these four control sites and to maintain normal blood pressure. Finally, local release of vasoactive substances from vascular endothelium may also be involved in the regulation of vascular resistance. For example, endothelin-1 (see Chapter 17) constricts and nitric oxide (see Chapter 19) dilates blood vessels. 

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