Smooth muscle control systems are illustrated in Figure 14.6 of this medical textbook excerpt. Both multiunit and single-unit smooth muscles can be influenced by neurotransmitters, hormones, or signaling molecules released by nerves, circulating or locally generated substances. These substances can either induce contraction or relaxation of the smooth muscle cells by activating specific receptors and increasing the concentration of cellular calcium. The response of the smooth muscle cells depends on the concentration of these neurotransmitters or hormones at the cell membrane and the nature of the receptors present. Hormone concentrations are influenced by factors such as diffusion distance, release, reuptake, and catabolism. Cells lacking close neuromuscular contacts will have a limited response to neural activity unless they are electrically coupled to transmit depolarization from cell to cell. Multiunit smooth muscles resemble striated muscles and rely on neural regulation for control. On the other hand, single-unit smooth muscles, similar to cardiac muscle, propagate electrical activity throughout the tissue. Most smooth muscles are likely to fall between these two ends of the single-unit-multiunit spectrum. The scanning micrograph of the rat small intestine shows varicose nerves with a scale bar of 3µm. In the fluorescent image of the guinea pig mesentery, catecholamines in single adrenergic axons are depicted with a scale bar of 10µm. Sympathetic nerves (in black) are associated with small arteries, large arterioles, small veins, large venules, small arterioles, and terminal arterioles in the vasculature. Capillaries, post-capillary venules, and small venules appear to lack sympathetic innervation. The predominant effect of sympathetic stimulation is smooth muscle contraction due to the abundance of α1-AR relative to β2-AR in smooth muscle. Activation of β2-AR on smooth muscle modulates the degree of smooth muscle contraction during sympathetic stimulation. Therapeutic β2-AR agonists are crucial for bronchial smooth muscle relaxation during asthmatic attacks. Vascular smooth muscles have poor innervation by the parasympathetic system. However, during vagal stimulation, acetylcholine (ACh) can become elevated in the coronary circulation, resulting in coronary relaxation through its binding to endothelial cells. It is important to note that this effect of ACh is indirect, as it leads to the release of the smooth muscle relaxant nitric oxide from the endothelial cells. In regions of the coronary circulation with damaged endothelium, binding of ACh to coronary smooth muscle could promote contraction (vasospasm) directly. Various hormones, including angiotensin II, vasopressin, endothelin, as well as neurotransmitters like norepinephrine and acetylcholine, can elevate InsP3 in smooth muscle and result in smooth muscle contraction. During periods of intense muscular activity, adenosine can be released from the working muscle, diffuse to the neighboring vasculature, and promote vasodilation. Adenosine acts as a local factor to increase blood flow to a specific region, such as the working muscle. The abbreviations used in the excerpt include AR (adrenergic receptor), EC (endothelial cell), InsP3 (inositol 1,4,5-trisphosphate), and SMC (smooth muscle cell).
Varicosity with neurotransmitter vesicles •Fig. 14.6 Controlsystemsofsmoothmuscle.Inbothmultiunitsmoothmuscle(A)andsingleunitsmoothmuscle(B),neurallyreleasedtransmittersorcirculatingorlocallygeneratedhormonesorsignalingmoleculescaninducecontractionorrelaxationofthesmoothmuscle.Thecombinationofaneurotransmitter,hormone,ordrugwithspecificreceptorsactivatescontractionbyincreasingcellCa++ .Theresponseofthecellsdependsontheconcentrationofthetransmittersorhormonesatthecellmembraneandthenatureofthereceptorspresent.Hormoneconcentrationsdependondiffusiondistance,release,reuptake,andcatabolism.Consequently,cellslackingcloseneuromuscularcontactswillhavealimitedresponsetoneuralactivityunlesstheyareelectricallycoupledsothatdepolarizationistransmittedfromcelltocell.A,Multiunitsmoothmusclesresemblestriatedmusclesinthatthereisnoelectricalcouplingandneuralregulationisimportant.B,Single-unitsmoothmusclesarelikecardiacmuscle,andelectricalactivityispropagatedthroughoutthetissue.Mostsmoothmusclesprobablyliebetweenthetwoendsofthesingleunit–multiunitspectrum.C,Scanningmicrographofvaricosenervelyingoverratsmallintestinescalebar= 3µm.D,Fluorescentimageofcatecholaminesinsingleadrenergicaxoninguineapigmesentery.Scalebar= 10µm.E,Depictionofdistributionofsympatheticnerves(in black) invasculature.Sympatheticnervesareassociatedwithsmallarteries(SA),largearterioles(la),smallveins(SV),largevenules(lv),smallarterioles(sa),andterminalarterioles(TA).Capillaries(c),post-capillaryvenules(pcv),andsmallvenules(svl)appeartolacksympatheticinnervation.(C,FromBurnstockG:Autonomicneuralcontrolmechanisms.Withspecialreferencetotheairways.InKalinerMA,BarnesPJ(Eds.),TheAirways.NeuralControlinHealthandDisease,MarcelDekker,NewYork(1988),pp.1–22.D,FromChamleyJH,MarkGE,CampbellGR,BurnstockG.(1972)Sympatheticgangliainculture.I.Neurons.Z.Zellforsch.Mikrosk.Anat.135,287-314.) aThepredominanteffectofsympatheticstimulationissmoothmusclecontractioncausedbytheabundanceofα1-ARrelativetoβ2-ARinsmoothmuscle.bActivationofβ2-ARonsmoothmusclemodulatesthedegreeofsmoothmusclecontractionduringsympatheticstimulation.Therapeuticβ2-ARagonistsareimportantfortherelaxationofbronchialsmoothmuscleduringasthmaticattacks.cVascularsmoothmusclesarepoorlyinnervatedbytheparasympatheticsystem.Duringvagalstimulation,however,acetylcholine(ACh)canbecomeelevatedinthecoronarycirculationandresultincoronaryrelaxation(mediatedbybindingofAChtoendothelialcells).NotethatthiseffectofAChisindirectbecausebindingofAChtoendothelialcellsresultsinreleaseofthesmoothmusclerelaxantnitricoxidefromtheendothelialcells.Inregionsofthecoronarycirculationwithdamagedendothelium,bindingofAChtocoronarysmoothmusclecouldpromotecontraction(vasospasm;directeffect).dAvarietyofhormonescanelevateInsP3insmoothmuscleandtherebyresultinsmoothmusclecontraction.SuchhormonesincludeangiotensinII,vasopressin,andendothelin,alongwiththeneurotransmittersnorepinephrineandacetylcholine.Asnotedabove,however,eachhormone/transmitterbindstoaspecificreceptortype.eDuringperiodsofintensemuscularactivity,adenosinecanbereleasedfromtheworkingmuscle,diffusetotheneighboringvasculature,andpromotevasodilation.Thus,adenosineisactingasalocalfactortoincreasebloodflowtoaspecificregion(i.e.,workingmuscle).AR,adrenergicreceptor;EC,endothelialcell;InsP3,inositol1,4,5-trisphosphate;SMC,smoothmusclecell.