Vascular smooth muscle, regulation

In addition to intracellular heme-containing proteins, big-conductance calcium-dependent K+ (BKCa) channels and calcium-spark activated transient Kca channels in plasma membrane are also tar geted by CO [3]. As well known, nitric oxide (NO) also activates BKca channels in vascular smooth muscle cells. While both NO and CO open BKCa channels, CO mainly acts on alpha subunit of BKCa channels and NO mainly acts on beta subunit of BKca channels in vascular smooth muscle cells. Rather than a redundant machinery, CO and NO provide a coordinated regulation of BKca channel function by acting on different subunits of the same protein complex. Furthermore, pretreatment of vascular smooth muscle... 

Human umbilical vein endothelial cells (HUVEC) express the isoforms ECE-la, -lb, -Id and ECE-2. In these cells, ET-1 is secreted via both a constitutive and a regulated pathway. The ratio of released ET-1 big-ET-1 is 4 1. About 80% of the ET-1 is secreted at the abluminal cell surface of endothelial cells. ECE-isoforms are abundantly expressed on the cell surface of endothelial cells and to a lower level also on vascular smooth muscle cells. In atherosclerotic lesions of vessels, however, ECE expression in smooth muscle cells is upregulated. ECE isoforms expressed in smooth muscle cells contribute significantly to the generation of mature ET in normal and in particular atherosclerotic vessels. 

Smooth muscles do more than contract and the regulation of the mitotic activity of vascular smooth muscle is important in the maintenance of the oxygen supply to tissues and the genesis of hypertension of non-renal origin. Secretion activities of smooth muscle are just beginning to be appreciated. 

Nitric oxide is a regulator of vascular smooth muscle blockage of its formation from arginine causes an acute elevation of blood pressure, indicating that regulation of blood pressure is one of its many functions. 

Apo E, apolipoprotein E CAD, coronary artery disease FKN, fractalkine MHC, major histocompatibility complex MCP-1, monocyte chemoattractant protein 1 MMPs, matrix metalloproteinases NK, natural killer oxLDL, oxidized LDL RANTES, regulated on activation, normal T cell expressed and secreted VSMCs, vascular smooth muscle cells. 

Blood pressure and electrolyte composition by regulating mechanisms involved with urine output, thirst, salt appetite, maintenance of plasma osmolarity, and vascular smooth muscle tone... 

Therefore, depending upon the degree of constriction of the vascular smooth muscle, these vessels may alter their diameter, and consequently their blood flow, across a very wide range. For this reason, the arterioles are the major resistance vessels in the circulatory system. In fact, the primary function of arterioles is to regulate the distribution of the cardiac output and to determine which tissues receive more blood and which receive less, depending upon the tissue s and the body s needs. 

Total peripheral resistance (TPR) is the resistance to blood flow offered by all systemic vessels taken together, especially by the arterioles, which are the primary resistance vessels. Therefore, MAP is regulated by cardiac activity and vascular smooth muscle tone. Any change in CO or TPR causes a change in MAP. The major factors that affect CO, TPR, and therefore MAP, are summarized in Figure 15.3, as well as in Table 15.1. These factors may be organized into several categories and will be discussed as such ... 

The sympathetic system also innervates vascular smooth muscle and regulates the radius of the blood vessels. All types of blood vessels except capillaries are innervated however, the most densely innervated vessels include arterioles and veins. An increase in sympathetic stimulation of vascular smooth muscle causes vasoconstriction and a decrease in stimulation causes vasodilation. Constriction of arterioles causes an increase in TPR and therefore MAP. Constriction of veins causes an increase in venous return (VR) which increases end-diastolic volume (EDV), SV (Frank-Starling law of the heart), CO, and MAP. 

Vasopressin also plays an important role in short-term regulation of blood pressure through its action on vascular smooth muscle. This hormone is the most potent known endogenous vasoconstrictor. Two types of vasopressin receptors have been identified V, receptors mediate vasoconstriction... 

A decrease in plasma volume leads to decreased MAP, which is detected by baroreceptors in the carotid sinuses and the arch of the aorta. By way of the vasomotor center, the baroreceptor reflex results in an overall increase in sympathetic nervous activity. This includes stimulation of the heart and vascular smooth muscle, which causes an increase in cardiac output and total peripheral resistance. These changes are responsible for the short-term regulation of blood pressure, which temporarily increases MAP toward normal. 

A role for the 5-HT7 receptor in the regulation of circadian rhythms has been implicated. As discussed above, 5-HT has been known for some time to induce phase shifts in behavioral circadian rhythms and modulate neuronal activity in the suprachiasmatic nucleus, the likely site of the mammalian circadian clock. The pharmacological characteristics of the effect of 5-HT on circadian rhythms are consistent with 5-HT7 receptor. Moreover, mRNA for the 5-HT7 receptor is found in the suprachiasmatic nucleus. There is also increasing evidence that the 5-HT7 receptor may play a role in psychiatric disorders. The regional distribution of 5-HT7 receptors in brain includes limbic areas and cortex. Atypical antipsychotics, such as clozapine and risperidone, and some antidepressants display high affinity for this receptor. In the periphery, 5-HT7 receptors havebeenshown to mediate relaxation of vascular smooth muscle. 

Welsh DG, Morielli AD, Nelson MT, Brayden JE 2002 Transient receptor potential channels regulate myogenic tone of resistance arteries. Circ Res 90 248-250 Xu SZ, Beech DJ 2001 TrpCl is a membrane-spanning subunit of store-operated Ca2+ channels in native vascular smooth muscle cells. Circ Res 88 84-87 Yamazawa T, lino M, Endo M 1992 Presence of functionally different compartments of the Ca2+ store in single intestinal smooth muscle cells. FEBS Lett 301 181—184... 

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