Alteration of Contractile Function and Calcium Ion Movements in Vascular Smooth Muscle by Gentamicin and Other Aminoglycoside Antibiotics

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

Large-conductance Ca2+-activated potassium (BKCa) channels are key determinants of vascular smooth muscle excitability. Impaired BKCa channel function through remodeling of BKCa β1 expression and function contributes to vascular complications in animal models of diabetes. Yet, whether similar alterations occur in native vascular smooth muscle from humans with type 2 diabetes is unclear. In this study, we evaluated BKCa function in vascular smooth muscle from small resistance adipose arteries of non-diabetic and clinically diagnosed type 2 diabetic patients. We found that BKCa channel activity opposes pressure-induced constriction in human small resistance adipose arteries, and this is compromised in arteries from diabetic patients. Consistent with impairment of BKCa channel function, the amplitude and frequency of spontaneous BKCa currents, but not Ca2+ sparks were lower in cells from diabetic patients. BKCa channels in diabetic cells exhibited reduced Ca2+ sensitivity, single-channel open probability and tamoxifen sensitivity. These effects were associated with decreased functional coupling between BKCa α and β1 subunits, but no change in total protein abundance. Overall, results suggest impairment in BKCa channel function in vascular smooth muscle from diabetic patients through unique mechanisms, which may contribute to vascular complications in humans with type 2 diabetes.

SCN − ions induce contraction of vascular muscle from male but not female rats

ARTICLESPhosphorylase, calcium, and cyclic AMP in smooth-muscle contractionJ DiamondJ DiamondPublished Online:01 Oct 1973https://doi.org/10.1152/ajplegacy.1973.225.4.930MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByBibliography16 October 2014Glycogen Metabolism in Smooth MuscleGlycogen Metabolism in Smooth MuscleThe direct excitatory effects of cimetidine on the smooth muscle of guinea pig ileumAgents and Actions, Vol. 11, No. 3Effects of Strontium as Substitute for Extracellular Calcium on Contraction and Relaxation of Vascular Smooth MusclePapaverine-Induced Inhibition of Electrical and Mechanical Activity and Calcium Movements of Rat Ileal Smooth Muscle1 June 1980 | Journal of Experimental Biology, Vol. 86, No. 1EFFECTS OF HYDRALAZINE AND VERAPAMIL ON PHOSPHORYLASE ACTIVITY AND GUANOSINE CYCLIC 3′,5′-MONOPHOSPHATE LEVELS IN GUINEA-PIG TAENIA COLI19 July 2012 | British Journal of Pharmacology, Vol. 68, No. 2Cytochemical demonstration of adenylate and guanylate cyclases in vascular smooth muscle of circle of WillisJournal of Neurosurgery, Vol. 49, No. 2Mechanisms of contractile response of cerebral artery to externally-applied fresh bloodJournal of Neurosurgery, Vol. 43, No. 1The role of cyclic nucleotides in central synaptic function21 June 2005The Role of Cyclic Nucleotides in Central Synaptic FunctionEnzymes of glycogen metabolism in developing embryos of a teleostWilhelm Roux's Archives of Developmental Biology, Vol. 177, No. 2Calcium regulation in the uterusPharmacology & Therapeutics. Part B: General and Systematic Pharmacology, Vol. 1, No. 4Response of single nephron glomerular filtration rate to distal nephron microperfusionKidney International, Vol. 6, 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. 6A Possible Regulatory Role of Mitochondrial Calcium Uptake in Uterine Contractions More from this issue > Volume 225Issue 4October 1973Pages 930-937 Copyright & PermissionsCopyright © 1973 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1973.225.4.930PubMed4355181History Published online 1 October 1973 Published in print 1 October 1973 Metrics

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.

In type 2 diabetes, in contrast to the well-documented endothelial dysfunction, studies assessing vascular smooth muscle (VSM) function have yielded discrepant results over the last two decades. We therefore sought to determine whether or not VSM function is impaired in individuals with type 2 diabetes. We conducted a systematic search of MEDLINE, Cochrane, Scopus and Web of Science databases, from their respective inceptions until December 2012, for articles evaluating VSM function in individuals with type 2 diabetes. A meta-analysis was performed to compare the standardised mean difference (SMD) in VSM function between individuals with type 2 diabetes and age-matched controls. Subgroup analyses and meta-regression were used to identify sources of heterogeneity. Twenty-seven articles (1,042 individuals with type 2 diabetes and 601 control subjects) were included in this analysis. VSM function was significantly impaired in diabetic compared with control subjects (SMD -0.68, 95% CI -0.84, -0.52; p < 0.001). Although moderate heterogeneity among studies was found (I (2) = 52%), no significant publication bias was detected. Subgroup analyses showed a further decline in VSM function assessed in the microcirculation compared with the macrocirculation of individuals with type 2 diabetes (p = 0.009). In meta-regression, VSM function in the microcirculation was inversely associated with BMI and triacylglycerols and was positively associated with HDL-cholesterol. In addition to the endothelium, the VSM is a source of vascular dysfunction in type 2 diabetes. An exacerbation of VSM function in the microcirculation may be a distinctive feature in type 2 diabetes.

This study investigated the effects of altered extracellular Ca2+ on in vitro femoral arterial smooth muscle responsiveness in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Compared with controls, femoral arteries from DOCA-salt rats showed a significant increase in sensitivity to KCl and norepinephrine in normal Ca2+ (2.5 mM). Although no difference in maximal contractile response to KCl was observed between groups, there was a significant difference in maximal response to norepinephrine. Dose-response curves in low Ca2+ (0.25 mM) resulted in a significant decrease in the sensitivity of femoral arteries from DOCA-salt rats to KCl and NE so that the responses were similar to those of controls. Relaxation of femoral arteries from DOCA-salt rats after washout of the KCl contraction was significantly slower than that of controls in both low and normal Ca2+. Isoproterenol-induced relaxation of femoral arteries from DOCA-salt rats was significantly attenuated in normal Ca2+. Sensitivity of femoral arteries from DOCA-salt rats to isoproterenol increased in low Ca2+, but maximal relaxation was unaltered. Whereas no difference in maximal relaxation to NaNO2 was seen in femoral arteries from either group in normal Ca2+, a significant decrease in sensitivity to NaNO2 was observed in femoral arteries from DOCA-salt rats. In low Ca2+ the response of femoral arteries from DOCA-salt rats to NaNO2 was similar to that of controls. These results suggest that the increased vascular smooth muscle responsiveness to KCl and norepinephrine seen in DOCA-salt hypertension is due to increased sensitivity of the vascular smooth muscle to Ca2+. Extracellular Ca2+, however, plays only a minor role in the decreased vasodilator responsiveness seen in this form of hypertension.

Notch receptors and ligands mediate heterotypic cell signaling that is required for normal vascular development. Dysregulation of select Notch receptors in mouse vascular smooth muscle (VSM) and in genetic human syndromes causes functional impairment in some regional circulations, the mechanistic basis of which is undefined. In this study, we used a dominant-negative Mastermind-like (DNMAML1) to block signaling through all Notch receptors specifically in VSM to more broadly test a functional role for this pathway in vivo. Mutant DNMAML1-expressing mice exhibited blunted blood pressure responses to vasoconstrictors, and their aortic, femoral, and mesenteric arteries had reduced contractile responses to agonists and depolarization in vitro. The mutant arteries had significant and specific reduction in the expression and activity of myosin light chain kinase (MLCK), a primary regulator of VSM force production. Conversely, activated Notch signaling in VSM cells induced endogenous MLCK transcript levels. We identified MLCK as a direct target of activated Notch receptor as demonstrated by an evolutionarily conserved Notch-responsive element within the MLCK promoter that binds the Notch receptor complex and is required for transcriptional activity. We conclude that Notch signaling through the transcriptional control of key regulatory proteins is required for contractile responses of mature VSM. Genetic or pharmacological manipulation of Notch signaling is a potential strategy for modulating arterial function in human disease.

In this issue of Diabetologia, a meta-analysis performed by Montero and co-authors (Diabetologia doi 10.1007/s00125-013-2974-1 ) demonstrates a significant impairment of vascular smooth muscle (VSM) function in type 2 diabetic patients. Endothelial function and VSM function between type 2 diabetic and healthy individuals were associated, especially in the microcirculation, confirming the hypothesis that unresponsiveness of VSM cells to NO may amplify the consequences of reduced NO availability. This study suggests a novel interpretation for endothelial dysfunction in diabetic patients, indicating VSM cells as key players. Causative mechanisms of VSM dysfunction, which seems to be a feature of the vascular phenotype of type 2 diabetes mellitus, are largely unexplored in humans. Future studies should also address the crucial issue of the prognostic significance of VSM dysfunction in diabetic patients, and possibly in other conditions characterised by high cardiovascular risk.

Objective To investigate the effect of hypoxia on endothelial growth factor (VEGF) expression in vascular intimal smooth muscle cells (VSMC) and function of VSMC of swine models of brain arteriovenous malformations (BAVM). Methods The stable swine models of BAVM were established; separation of cerebral microvascular network (RM) was performed and VSMC was selected and primarily cultured. VSMC from the above models and normal swines were divided into four groups: group A, VSMC from normal swines cultured at 21% O2; group B, VSMC from models cultured at 21% O2; group C, VSMC from normal swines cultured at 1% O2; group D, VSMC from models cultured at 1% O2. Quantitative real-time polymerase chain reaction (RT-PCR) and Western blotting were used to validate the mRNA and protein VEGF expressions in VSMC; TUNNEL was used to detect the apoptosis of VSMC, and Transwell assay was used to determine the VSMC invasion. Results (1) VSMC density in the four groups was 71.65±4.22, 158.24±9.87, 95.33±7.21 and 299.80±13.23 cells/field in group A-D, with significant differences (F=119.351, P=0.000). (2) VEGF mRNA expression quantity in the four groups was 1.93±0.77, 4.51±1.25, 2.87±1.94 and 8.03±1.74 in group A-D, with significant differences (F=119.351, P=0.000); that in group B-D was significantly higher than that in group A (P 0.05); at the 72 h, the number of apoptosis and invasion cells in group A was significantly decreased as compared with those in group B, C and D (P<0.05). Conclusion Hypoxia can increase the VEGF expression, aggravate the apoptosis and invasion of VSMC, and accelerate the formation of vascular malformation in BAVM models. Key words: Hypoxia; Endangium; Vascular smooth muscle cell; Vascular endothelial growth factor

Insulin resistance does not impair contractile responses of cerebral arteries

Objective: Hyperpolarizing large-conductance calcium-activated potassium channels are important modulators of vascular smooth muscle and endothelial cell function. In vascular smooth muscle cells MK is composed of pore forming alpha-subunits and modulatory beta-subunits. However, the expression and composition of MK subunits in endothelium has not been studied so far. We investigated MK in human and porcine endothelial cells using patch-clamp techniques, RT-PCR and sequencing. Methods: We performed patchclamp experiments in EA.hy 926, a human permanent endothelial cell line, in human umbilical vein endothelial cells (HUVEC), in porcine aortic (PAEC), and in porcine renal endothelial cells. RNA was prepared and RT-PCR was done by using specific olignucleotides. To verify the function of the primers we took cDNA from vascular smooth muscle cells. Sequencing was performed to analyse the amplified fragments of the subunits of MK. Results: RT-PCR with cDNA from vascular smooth muscle cells and sequence analysis indicated that the oligonucleotide primer amplified the alpha- and beta-subunit. After reverse transcription and amplification by PCR we obtained an alpha-fragment for EA.hy 926, HUVEC, PAEC and PREC. In contrast, no beta-fragment could be amplified in EC. Correspondingly, the MK opener DHS-I stimulating BK only in the presence of the betasubunit, had no effect on BK in endothelium, whereas the alpha-subunit selective MK opener NS1619 markedly increased channel activity. Conclusions: The lack of the modulatory beta-subunit indicates a substantially different channel regulation in endothelial cells compared to vascular smooth muscle cells.

Role of NO in vascular smooth muscle and cardiac muscle function

Dysfunction of ion handling, including binding and fluxes (passive and active transport) of physiologically important ions such as potassium, sodium, calcium, and magnesium, by vascular smooth muscle cell membranes has repeatedly been reported to be associated with the pathophysiology of hypertension. The specific purpose of this review is to summarize and evaluate the evidence for alterations of calcium ion (Ca2+) handling by vascular smooth muscle in various forms of hypertension in the animal model on the basis that regulation of cytoplasmic Ca2+ concentration is a complex and yet vitally important process for a normal function of vascular smooth muscle and that derangement of such a regulation may result in excessive retention of cytoplasmic Ca2+, contribute toward increase of total peripheral resistance, and ultimately lead to elevation of blood pressure. Emphasis is placed upon the consideration of the usefulness of the subcellular membrane fractionation technique in studies of binding and transport of Ca2+ by vascular and nonvascular smooth muscle membranes from genetic as well as experimental hypertensive rats. The limitations of the interpretation of data using such an approach are also considered. Decreased active transport of Ca2+ across isolated plasma membrane vesicles from large and small arteries occurs in several but not all forms of hypertension. This membrane abnormality also occurs in nonvascular smooth muscles and other tissues or cells not confined to the cardiovascular system in genetic hypertension, but not in experimental hypertension. A hypothesis of general membrane defects in spontaneous hypertension is proposed.(ABSTRACT TRUNCATED AT 250 WORDS)

Vascular smooth muscle contractile properties in the turtle Pseudemys scripta elegans