Vascular smooth muscle, nitric oxide

Smooth muscle Nitric oxide is a powerful vasodilator in all vascular beds and a potent relaxant in most other smooth muscle tissues. The mechanism of this effect involves activation of guanylyl cyclase and the synthesis of cGMP. cGMP in turn facilitates the dephosphorylation and inactivation of myosin light chains, which results in relaxation of the muscle cells. Nitric oxide plays a physiologic role in erectile tissue function, in which smooth muscle relaxation is required to bring about the influx of blood that causes erection. 

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... 

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. 

The vascular endothelium produces a number of substances that are released basally into the blood vessel wall to alter vascular smooth muscle tone. One such substance is endothelin (ET-1). Endothelin exerts its effects throughout the body, causing vasoconstriction as well as positive inotropic and chronotropic effects on the heart. The resulting increases in TPR and CO contribute to an increase in MAP. Synthesis of endothelin appears to be enhanced by many stimuli, including Ag II, vasopressin, and the mechanical stress of blood flow on the endothelium. Synthesis is inhibited by vasodilator substances such as prostacyclin, nitric oxide, and atrial natriuretic peptide. There is evidence that endothelin is involved with the pathophysiology of many cardiovascular diseases, including hypertension, heart failure, and myocardial infarction. Endothelin receptor antagonists are currently available for research use only. 

NO is a gaseous neurotransmitter implicated in signaling in the central and peripheral nervous system as well as in the immune system and the vasculature. NO is formed from L-arginine by nitric oxide synthase (NOS). There are three isoforms of NOS. All isoforms require NADPH as a cofactor, use L-arginine as a substrate, and are inhibited by Nw-nitro-L-arginine methyl ester (L-NAME). The three isoforms are separate gene products. One isoform of NOS is a cytosolic, calcium/calmodulin-independent, inducible enzyme (iNOS). It is found in macrophages, neutrophils, vascular smooth muscle, and endothelia. The iNOS... 

Activation of brain H receptors also stimulates cGMP synthesis [19]. Outside the brain, histamine is known to relax vascular smooth muscle by activation of endothelial H receptors, thereby increasing endothelial Ca2+ concentrations and stimulating the synthesis and release of nitric oxide. The latter, a diffusible agent, then activates the smooth muscle guanylyl cyclase [30]. Although less is known about these mechanisms in the CNS, there is evidence that brain H receptor activation can produce effects that depend on guanylyl cyclase activity [19]. 

While several studies reported that PLB was present in smooth muscle, very little was known about its role in Ca2+ handling. Some evidence suggested that in addition to A-kinase pathway phosphorylation, activation of the G -kinase pathway was associated with PLB phosphorylation. The latter was of particular interest to vascular smooth muscle, for which endothelium-dependent relaxation via nitric oxide (NO) made the mechanism of G-kinase-mediated relaxation of considerable physiological significance (Karczewski et al 1998). 

Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside, and nitric oxide evidence for the involvement of S-nitrosothiols as active intermediates. /. Pharmacol. Exp. Then 218 (1981), p. 739-749... 

Benjamin, N., Dutton, J. A. E., Ritter, J. M., Human vascular smooth muscle cells inhibit platelet aggregation when incubated with glyceryl trinitrate evidence for generation of nitric oxide. Br. J. Pharmacol. 102 (1991), p. 847-850... 

Feelisch, M., Kelm, M., Biotransformation of organic nitrates to nitric oxide by vascular smooth muscle and endothelial cells. Biochem. 

Seth, P., Fung, H-L., Biochemical characterization of a membrane-bound enzyme responsible for generating nitric oxide from nitroglycerin in vascular smooth muscle cells. Biochem. Pharmacol. 46... 

Buchwalow IB, Podzuweit T, Bocker W, Samoilova VE, Thomas S, Wellner M, Baba HA, Robenek H, Schnekenburger J, Lerch MM (2002) Vascular smooth muscle and nitric oxide... 

Nitric oxide (NO) is synthesized by vascular endothelium in response to vasodilators. It diffuses into the surrounding vascular smooth muscle, where it directly binds the heme group of soluble guanylate cyclase, activating the enzyme. 

Answer C. Nitroprusside is metabolized to produce nitric oxide, NO, normally produced by the vascular endothelium, stimulates the cyclase in vascular smooth muscle to increase cGMP, activate protein kinase G, and cause relaxation. 

Chang, T., Wang, R., and Wu, L. (2005). Methylglyoxal-induced nitric oxide and peroxyni-trite production in vascular smooth muscle cells. Free Radic. Biol. Med. 38, 286-293. 

The vasodilatory effect of Hi-receptor stimulation is mainly due to an endothelial release of nitric oxide, which is able to activate the soluble guany-late cyclase in vascular smooth muscle cells. This effect is mainly responsible for the erythema seen after injection (insect sting) of histamine. Furthermore, it is responsible, together with the increased capillary permeability, for the cardiovascular symptoms seen in anaphylactic or allergic shock. 

Fig. 1. The EDRF/NO pathway in vascular smooth muscle. Vasodilatation by nitrates at a cellular level. Nitrates, nitrites, and nitroprusside-Na are able to release nitric oxide (NO), which stimulates the conversion of GTP into cyclic guanosine monophosphate (cGMP), thus causing vasodilatation. The release of EDRF (=NO) from endothelial cells can be stimulated by various endogenous compounds. Endogenous EDRF (=NO) then causes vasodilatation, similar to the NO released by...

Vascular endothelium also plays an important role in maintaining vascular tone. The endothelium can modulate both vasodilation and vasoconstriction through its ability to locally synthesize and release vasodilators such as nitric oxide, endothehum-derived hyperpolarizing factor, and PGI2, and vasoconstrictors such as endothehn, which in turn directly affect vascular smooth muscle activity. Stimulation of az-adrenoceptors located on the endothelial cells in certain vascular beds (such as the coronary artery) results in the release of nitric oxide and vasodilation. 

Physiological sites proposed for nitric oxide action include the immune system, where nitric oxide acts as a cytostatic agent, is tumoricidal, and can inhibit viral replication. In the cardiovascular system, nitric oxide is the biological mediator of vasodilator responses to agents such as acetylcholine and bradykinin, which act as receptors on endothelial cells to activate NOS and stimulate nitric oxide production. Diffusible nitric oxide then activates guanylate cyclase in vascular smooth muscle cells, leading to the production of cyclic guano-sine monophosphate (GMP) and vasodilation. In the brain, stimulation of A-methyl-o-aspartate receptors on... 

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