Ultrastructure, function and composition of smooth muscle.

The importance of Ca2+calmodulin-dependent myosin light chain kinase (MLCK) for smooth muscle contraction is well documented.1 Until recently, myosin light chain (MLC) phosphatase was thought to be unregulated and constitutively active. However, studies have demonstrated that smooth muscle contraction is dependent on regulation of MLC phosphatase activity.2,3⇓ The inhibition of phosphatase activity increases force at a constant [Ca2+], whereas a stimulation of MLC phosphatase activity reduces force at a constant [Ca2+]. MLC phosphatase isolated from smooth muscle is a holoenzyme consisting of 3 subunits2: a small ≈20-kDa subunit, an ≈38-kDa catalytic subunit, and a myosin-targeting subunit (MYPT) of 110 to 133 kDa. The small subunit has no established function and is not required for either catalytic activity or activation of PP1c.2 The catalytic subunit is a PP1c phosphatase, and the δ isoform is associated with the holoenzyme.4 The large subunit is the MYPT. Isoform diversity of MYPT was first shown in chicken where 2 isoforms (M130 and M133)2 were shown to differ by the presence of a central insert between aa residues 512 to 552.5 Similar isoform diversity has been demonstrated for MYPT isolated from other species.2,6⇓ In addition to the isoform diversity produced by the central insert, alternative splicing of a COOH-terminal exon leads to MYPT isoforms, which differ by the presence or absence of a leucine zipper.7 At any intracellular [Ca+2], force for an agonist stimulated contraction is higher than for depolarization.8,9⇓ This phenomenon has been …

Mechanisms of action of transmitters and other substances on smooth muscle.

Nimodipine inhibits intestinal and aortic smooth muscle contraction by regulating Ca2+-activated Cl− channels

Vascular endothelial growth factor (VEGF) is a potent and specific mitogen for vascular endothelial cells and promotes neovascularization in vivo. To determine whether interleukin-1 beta (IL-1 beta), which is present in atherosclerotic lesions, induces VEGF gene expression in vascular smooth muscle cells, we performed RNA blot analysis on rat aortic smooth muscle cells (RASMC) with a rat VEGF cDNA probe. IL-1 beta increased VEGF mRNA levels in RASMC in a time- and dose-dependent manner. As little as 0.1 ng/ml IL-1 beta increased VEGF mRNA levels by 2-fold and 10 ng/ml IL-1 beta increased VEGF mRNA by 4-fold. We also measured the half-life of VEGF mRNA and performed nuclear run-on experiments before and after addition of IL-1 beta to see if IL-1 beta increased VEGF mRNA levels by stabilizing the mRNA or by increasing its rate of transcription. The normal, 2-h half-life of VEGF mRNA in RASMC was lengthened to 3.2 h (60%) by IL-1 beta, and IL-1 beta increased the rate of VEGF gene transcription by 2.1-fold. In immunoblot experiments with an antibody specific for VEGF, we found that IL-1 beta increased VEGF protein levels in RASMC by 3.3-fold. Together these data indicate that IL-1 beta induces VEGF gene expression in smooth muscle cells. This IL-1 beta-induced expression of VEGF may accelerate the progression of atherosclerotic lesions by promoting the development of new blood vessels.

pressure-induced (myogenic) constriction of arterioles is believed to be a fundamental contributor to the local regulation of microvascular blood flow and pressure. Myogenic constriction provides a level of tone upon which vasodilators can act to lower resistance and match blood flow to metabolic

ARTICLESDissociation by lanthanum of smooth muscle responses to potassium and acetylcholineFR Goodman, and GB WeissFR Goodman, and GB WeissPublished Online:01 Mar 1971https://doi.org/10.1152/ajplegacy.1971.220.3.759MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByInterference of pentobarbitone with the contraction of vascular smooth muscle in goat middle cerebral artery12 April 2011 | Journal of Pharmacy and Pharmacology, Vol. 33, No. 1Metronidazole-induced myocardial depression: chemical and pharmacological studies on the role of calcium in-vitro12 April 2011 | Journal of Pharmacy and Pharmacology, Vol. 37, No. 3Contractile Action of Mn2+ via Ca2+ Channels Activated by Bay K 8644 in Guinea-pig Taenia Coli12 April 2011 | Journal of Pharmacy and Pharmacology, Vol. 50, No. 4Historical techniques: Cytosolic Ca2+ and contraction in smooth muscleTrends in Pharmacological Sciences, Vol. 25, No. 7The action of calcium antagonists on Ca2+ movements in isolated vesselsHistaminergic effect of crude papaya latex on isolated guinea pig ileal stripsPhytomedicine, Vol. 11, No. 1Calcium antagonistic activity of Bacopa monniera on vascular and intestinal smooth muscles of rabbit and guinea-pigJournal of Ethnopharmacology, Vol. 66, No. 2Use of Lanthanum as a Tool to Delineate Calcium Mobilization Patterns in Smooth MuscleIon Channels as Targets for DrugsMuscle Relaxant Effects of a talantia roxburghiana on Intestinal Smooth Muscle27 September 2008 | International Journal of Pharmacognosy, Vol. 33, No. 2Inhibition of calcium-dependent contractions of the isolated guinea-pig ileal longitudinal muscle and taenia coli by the total glycosidic extract of the plant Sarcolobus globosusToxicon, Vol. 31, No. 1Effects of depolarizing concentrations of K+ and reduced osmotic pressure on 45Ca2+ accumulation by the rostral pars distalis of the tilapia (Oreochromis mossambicus)General and Comparative Endocrinology, Vol. 77, No. 2Interactions of Lanthanides with Tissues, Cells, and Cellular OrganellesRole of different calcium pools in the contraction of respiratory smooth muscleActa Physiologica Scandinavica, Vol. 124, No. 1Calcium channels in smooth muscleGastroenterology, Vol. 87, No. 4Time course of the spasmolytic effect of cadmium and cadmium uptake in guinea-pig taenia coliGeneral Pharmacology: The Vascular System, Vol. 15, No. 12 Calcium and Histamine Secretion from Mast CellsEFFECT OF LANTHANIDE IONS ON HISTAMINE SECRETION FROM RAT PERITONEAL MAST CELLS19 July 2012 | British Journal of Pharmacology, Vol. 72, No. 2The use of lanthanum and cytochalasin B to study calcium effects on skeletal muscle differentiation in vitroJournal of Cellular Physiology, Vol. 105, No. 3Differences in contractile responses to acetylcholine and serotonin in rat stomach fundus stripsEuropean Journal of Pharmacology, Vol. 65, No. 2-3Modification of Membrane Function by DrugsThe role of calcium and cyclic AMP in the contractile action of angiotensin II upon rat descending colonEuropean Journal of Pharmacology, Vol. 60, No. 2-3Methods of Measuring Intracellular CalciumModification of Membrane Function by DrugsCalcium Source for Contractile Response of Guinea Pig Taenia Caecum to Carbachol in a Calcium Deficient, Potassium Rich SolutionJapanese Journal of Pharmacology, Vol. 28, No. 4Interactions of Potassium, Noradrenaline and Acetylcholine in the Guinea Pig Vas DeferensActa Physiologica Scandinavica, Vol. 101, No. 4PROCEEDINGS OF THE British Pharmacological Society19 July 2012 | British Journal of Pharmacology, Vol. 61, No. 1EFFECTS OF DILTIAZEM AND LANTHANUM ION ON THE POTASSIUM CONTRACTURE OF ISOLATED GUINEA PIG SMOOTH MUSCLEJapanese Journal of Pharmacology, Vol. 27, No. 3EFFECTS OF SAMMARIUM (Sm3+) ON THE CONTRACTILITY OF ISOLATED GUINEA PIG VENTRAL TAENIA COLI TO HISTAMINEJapanese Journal of Pharmacology, Vol. 27, No. 4Investigation of the nature of differences between ?-adrenergic receptorsBulletin of Experimental Biology and Medicine, Vol. 79, No. 5Diphasic action of lanthanum in rat uterusPharmacological Research Communications, Vol. 7, No. 2Direct myocardial depressant effects of gentamicinEuropean Journal of Pharmacology, Vol. 30, No. 2The role of cyclic nucleotides in central synaptic function21 June 2005The Role of Cyclic Nucleotides in Central Synaptic FunctionCalcium regulation in the uterusPharmacology & Therapeutics. Part B: General and Systematic Pharmacology, Vol. 1, No. 4Alteration of Contractile Function and Calcium Ion Movements in Vascular Smooth Muscle by Gentamicin and Other Aminoglycoside AntibioticsAntimicrobial Agents and Chemotherapy, Vol. 5, No. 6Effects of Lanthanum on the Coupling between Membrane Excitation and Contraction of Isolated Frog Muscle FibresActa Physiologica Scandinavica, Vol. 90, No. 1Effect of lanthanum on 45Ca flux and secretion of protein from rat exocrine pancreasLife Sciences, Vol. 13, No. 7Quantitative aspects of drug-receptor interactionsJournal of Theoretical Biology, Vol. 40, No. 1The relaxing effect of aluminum and lanthanum on rat and human gastric smooth muscle in vitroEuropean Journal of Pharmacology, Vol. 22, No. 2Alterations in45Ca distribution and movements in ileal longitudinal smooth muscleAgents and Actions, Vol. 2, No. 5Effect of lanthanum on catecholamine release from adrenal medullaLife Sciences, Vol. 11, No. 20MEMBRANAL Ca++ TRANSLOCATION AND CHOLINERGIC RECEPTOR ACTIVATION More from this issue > Volume 220Issue 3March 1971Pages 759-766 Copyright & PermissionsCopyright © 1971 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1971.220.3.759PubMed4993569History Published online 1 March 1971 Published in print 1 March 1971 Metrics

Inhibitory effect of type 1 collagen gel containing α-elastin on proliferation and migration of vascular smooth muscle and endothelial cells

In the lesions of atherosclerosis, vascular smooth muscle cells (SMC) display many functions characteristic of cytokine activation that likely contribute importantly to ongoing inflammation during human atherogenesis. The transcription factor nuclear factor kappa-B (NFkappaB) often mediates the effects of cytokines on target cells, but the identity of Rel family members important in human SMC activation remains uncertain. In vitro, human SMC express multiple Rel family members. Of these, dimers of p65 and p50, but not a putative SMC-Rel, comprise basal and inducible NFkappaB binding activities. SMC express two inhibitor proteins IkappaBbeta and IkappaBalpha. Interleukin-1beta stimulation caused transient loss of IkappaBalpha and a sustained decrease of IkappaBbeta that correlated with increased and persistent levels of p65/p50 protein and binding activity in the nucleus. SMC cultured under serum-free conditions displayed little NFkappaB activity, but addition of serum or platelet-derived growth factor did activate NFkappaB. In situ analyses showed no evidence for basal NFkappaB activity in SMC in vivo as nonatherosclerotic arteries did not contain nuclear p65 or p50 protein. However, the nuclei of intimal SMC within human atheroma did contain both Rel proteins. We conclude that (i) dimers of p65 and p50, but not SMC-Rel, comprise NFkappaB complexes in human SMC; (ii) stimulatory components in serum activate NFkappaB and likely account for previously reported "constitutive" NFkappaB activity in cultured SMC; and (iii) exposure to inflammatory cytokines may produce prolonged NFkappaB activation in SMC because of sustained decreases in the inhibitory subunit IkappaB-beta.

Prevention of stenosis after vascular reconstruction: Pharmacologic control of intimal hyperplasia — A review

MDM2: A Novel Mineralocorticoid-Responsive Gene Involved in Aldosterone-Induced Human Vascular Structural Remodeling

Coronary microvascular function and blood flow responses during acute exercise are impaired in the aged heart but can be restored by exercise training. Coronary microvascular resistance is directly dependent on vascular smooth muscle function in coronary resistance arterioles; therefore, we hypothesized that age impairs contractile function and alters the phenotype of vascular smooth muscle in coronary arterioles. We further hypothesized that exercise training restores contractile function and reverses age-induced phenotypic alterations of arteriolar smooth muscle. Young and old Fischer 344 rats underwent 10 wk of treadmill exercise training or remained sedentary. At the end of training or cage confinement, contractile responses, vascular smooth muscle proliferation, and expression of contractile proteins were assessed in isolated coronary arterioles. Both receptor- and non-receptor-mediated contractile function were impaired in coronary arterioles from aged rats. Vascular smooth muscle shifted from a differentiated, contractile phenotype to a secretory phenotype with associated proliferation of smooth muscle in the arteriolar wall. Expression of smooth muscle myosin heavy chain 1 (SM1) was decreased in arterioles from aged rats, whereas expression of phospho-histone H3 and of the synthetic protein ribosomal protein S6 (rpS6) were increased. Exercise training improved contractile responses, reduced smooth muscle proliferation and expression of rpS6, and increased expression of SM1 in arterioles from old rats. Thus age-induced contractile dysfunction of coronary arterioles and emergence of a secretory smooth muscle phenotype may contribute to impaired coronary blood flow responses, but arteriolar contractile responsiveness and a younger smooth muscle phenotype can be restored with late-life exercise training. NEW & NOTEWORTHY Aging impairs contractile function of coronary arterioles and induces a shift of the vascular smooth muscle toward a proliferative, noncontractile phenotype. Late-life exercise training reverses contractile dysfunction of coronary arterioles and restores a young phenotype to the vascular smooth muscle.

Ins(1,4,5) P3 receptor regulation during ‘quantal’ Ca 2+ release in smooth muscle

Hyperglycemia has been implicated in the pathogenesis of both micro- and macrovascular complications in diabetes. Little is known, however, about glucose transporters and their regulation in the vascular system. In this study, the regulation of glucose transporters by glucose was examined in cultured BAECs and BSMCs, and in human arterial smooth muscle cells. Both BAECs and BSMCs transported glucose via the facilitated diffusion transport system. Glucose-transport activity in vascular smooth muscle cells was inversely and reversibly regulated by glucose. Exposure of BSMCs and HSMCs to high glucose decreased Vmax for 2DG and 3-O-MG uptake, whereas Km remained unchanged. The hexose-transport system of BAECs exhibited lower 2DG and 3-O-MG uptake compared with BSMCs and showed little or no adaptation to changes in ambient glucose. Northern blot analysis demonstrated that GLUT1 mRNA levels in BAECs and BSMCs were unaffected by the concentration of glucose in the medium. GLUT2-5 mRNA could not be detected by Northern blot analysis. GLUT1 protein, quantified by Western blot analysis, was more abundant in BSMCs than in BAECs and was decreased by approximately 50% when medium glucose was elevated from 1.2 to 22 mM for 24 h. The alterations in the level of GLUT1 protein correlated with the changes observed in transport activity. These observations suggest differential regulation of glucose transporter in response to glucose between smooth muscle and endothelial cells. The sites of autoregulation may involve translational control and/or the stability of the protein in the smooth muscle cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Autophagy in Atherosclerosis: Not All Foam Cells Are Created Equal.

Cultured bovine aortic smooth muscle (BASM) and endothelial (BAE) cells, like articular chondrocytes, synthesize two populations of small chondroitin/dermatan sulfate (CS/DS) proteoglycans (PGs) of similar size as PG-I/biglycan and PG-II/decorin. However, Northern blot analyses demonstrated that BAE cells express detectable amounts of mRNA transcripts only for PG-I/biglycan, whereas BASM cells and articular chondrocytes express mRNA transcripts for both PG-I/biglycan and PG-II/decorin. Endothelial cells from human umbilical vein also expressed detectable amounts of mRNA transcripts only for PG-I/biglycan, and not PG-II/decorin. Antiserum raised against bovine PG-II/decorin immunoprecipitated an apparent single PG species with relative molecular mass (Mr) of approximately 120,000-180,000 from BASM cell and articular chondrocyte cultures but failed to immunoprecipitate an equivalent PG species from BAE cell cultures, consistent with the results from Northern blot analysis. In contrast, immunoprecipitations by antisera to PG-I/biglycan indicated that cultured endothelial cells synthesize two forms of PG-I/biglycan with Mr values slightly larger than 200,000 and 120,000-140,000. It is likely, based on the magnitude of the size difference, that these two forms of PG-I/biglycan differ in the number of glycosaminoglycan chains. Additionally, BASM but not BAE cells were found to express detectable amounts of mRNA transcripts for type I collagen. The above results indicate that the two main cell types of the vascular wall, endothelial and smooth muscle cells, express different sets of small interstitial CS/DS PGs and that the synthesis of PG-II/decorin by these cells correlates with the expression of type I collagen, a collagen known to interact specifically with this PG. These differences in the expression of extracellular matrix molecules may be important in regulating the cell type-specific functions of endothelial and smooth muscle cells within the vascular tissue.