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Dissecting out the Complex Ca2+-Mediated Phenylephrine-Induced Contractions of Mouse Aortic Segments

Paul Fransen, Cor E. Van Hove, Arthur J. A. Leloup, Wim Martinet, Guido R. Y. De Meyer, Katrien Lemmens, Hidde Bult, Dorien M. Schrijvers, Agustin Guerrero-Hernandez
2015 PLoS ONE  
L-type Ca 2+ channel (VGCC) mediated Ca 2+ influx in vascular smooth muscle cells (VSMC) contributes to the functional properties of large arteries in arterial stiffening and central blood pressure regulation. How this influx relates to steady-state contractions elicited by α1adrenoreceptor stimulation and how it is modulated by small variations in resting membrane potential (V m ) of VSMC is not clear yet. Here, we show that α1-adrenoreceptor stimulation of aortic segments of C57Bl6 mice with
more » ... henylephrine (PE) causes phasic and tonic contractions. By studying the relationship between Ca 2+ mobilisation and isometric tension, it was found that the phasic contraction was due to intracellular Ca 2+ release and the tonic contraction determined by Ca 2+ influx. The latter component involves both Ca 2+ influx via VGCC and via non-selective cation channels (NSCC). Influx via VGCC occurs only within the window voltage range of the channel. Modulation of this window Ca 2+ influx by small variations of the VSMC V m causes substantial effects on the contractile performance of aortic segments. The relative contribution of VGCC and NSCC to the contraction by α1-adrenoceptor stimulation could be manipulated by increasing intracellular Ca 2+ release from noncontractile sarcoplasmic reticulum Ca 2+ stores. Results of this study point to a complex interactions between α1-adrenoceptor-mediated VSMC contractile performance and Ca 2+ release form contractile or non-contractile Ca 2+ stores with concomitant Ca 2+ influx. Given the importance of VGCC and their blockers in arterial stiffening and hypertension, they further point toward an additional role of NSCC (and NSCC blockers) herein. Fig 3. Effects of VGCC blockers on isometric contractions by PE. Nifedipine, verapamil and diltiazem partly inhibit isometric contractions induced by 1 μM PE in organ bath-mounted aortic segments. A) Contractions induced by 1 μM PE after incubating the segments with 1 to 100 nM nifedipine (n = 4); B) Ca 2+ channel blocker (CCB) concentration-response curves for the inhibition of contractions induced by 1 μM PE.
doi:10.1371/journal.pone.0121634 pmid:25803863 pmcid:PMC4372603 fatcat:xyjqvxgfijhgjb62ltyomxduha

Continuous administration of the mTORC1 inhibitor everolimus induces tolerance and decreases autophagy in mice

Ammar Kurdi, Mireille De Doncker, Arthur Leloup, Hugo Neels, Jean-Pierre Timmermans, Katrien Lemmens, Sandra Apers, Guido R Y De Meyer, Wim Martinet
2016 British Journal of Pharmacology  
BACKGROUND AND PURPOSE Everolimus is an allosteric inhibitor of the mechanistic target of rapamycin complex 1 (mTORC1) widely known for its potent autophagy stimulating properties. Because everolimus shows poor solubility and stability in aqueous solutions, long-term in vivo administration in preclinical models is challenging. The aim of the present study was to evaluate the effects of short-term and long-term everolimus administration on mTORC1 inhibition and autophagy induction in mice.
more » ... MENTAL APPROACH We developed a vehicle in which everolimus was solubilized and stable at 37°C for at least 1 month. Using osmotic minipumps, GFP microtubule-associated protein light chain 3 transgenic mice were treated continuously either with vehicle or everolimus (1.5 mg·kg À1 per day) for 3 or 28 days. Alternatively, a regimen consisting of intermittent everolimus administration (every other day) for 56 days by oral gavage was used. Autophagy markers and mTORC1 activation status were investigated in the liver. KEY RESULTS As expected, everolimus inhibited mTORC1 and stimulated autophagy in the liver after 3 days of treatment. However, continuous administration for 28 days resulted in hyperactivation of the Akt1-mTORC1 pathway accompanied by a remarkable decrease in autophagy markers. Everolimus given intermittently for 56 days partially rescued mTORC1 sensitivity to the drug but without inducing autophagy. The failure to induce autophagy following long-term everolimus administration was due to uncoupling of the mTORC1 substrate unc-51 like autophagy activating kinase 1. CONCLUSIONS AND IMPLICATIONS Our data encourage the use of intermittent everolimus regimens to prevent tolerance and to extend its activity. Abbreviations ACTB, β-actin; LC3, microtubule-associated protein light chain 3; mTORC1/2, mechanistic target of rapamycin, complex 1/2; RCC, renal cell carcinoma; p70S6K, ribosomal protein S6 kinase B1; S6rp, S6 ribosomal protein; SQSTM1, sequestosome 1; ULK1, unc-51 like autophagy activating kinase
doi:10.1111/bph.13626 pmid:27638766 pmcid:PMC5738667 fatcat:cst4sjjxqbbobjgfi6uiecveqa

Endothelial Senescence Contributes to Heart Failure With Preserved Ejection Fraction in an Aging Mouse ModelCLINICAL PERSPECTIVE

Andreas B. Gevaert, Hadis Shakeri, Arthur J. Leloup, Cor E. Van Hove, Guido R.Y. De Meyer, Christiaan J. Vrints, Katrien Lemmens, Emeline M. Van Craenenbroeck
2017 Circulation: Heart Failure  
doi:10.1161/circheartfailure.116.003806 pmid:28611124 fatcat:nolp2rxzpzc25helwelrvd6i7m

Exploring, exploiting and evolving diversity of aquatic ecosystem models: a community perspective

Annette B. G. Janssen, George B. Arhonditsis, Arthur Beusen, Karsten Bolding, Louise Bruce, Jorn Bruggeman, Raoul-Marie Couture, Andrea S. Downing, J. Alex Elliott, Marieke A. Frassl, Gideon Gal, Daan J. Gerla (+27 others)
2015 Aquatic Ecology  
. (| |Lemmen et al. 2011; Lemmen and Wirtz 2014).  ... 
doi:10.1007/s10452-015-9544-1 fatcat:u37bpbb46vfelpjmo3porjlpuq

Page 14 of Geoscience Canada Vol. 24, Issue 3 [page]

1997 Geoscience Canada  
Wheaton, E.E. and Arthur, L.M., 1989, Execu- tive summary, in Wheaton, E.E. and Arthur, L.M., eds., Environmental and Economic Impacts of the 1988 Drought: with Empha- sis on Saskatchewan and Manitoba:  ...  , D.S., in press, Moni- toring of sand dune activity in the Great Sand Hills, southwest Saskatchewan, in Lemmen, D.S. and Vance, R.E., eds., Holo- cene Climate and Environmental Changes in the Palliser  ... 

Personalized management of elderly patients with rectal cancer: Expert recommendations of the European Society of Surgical Oncology, European Society of Coloproctology, International Society of Geriatric Oncology, and American College of Surgeons Commission on Cancer

Isacco Montroni, Giampaolo Ugolini, Nicole M. Saur, Antonino Spinelli, Siri Rostoft, Monica Millan, Albert Wolthuis, Ian R. Daniels, Roel Hompes, Marta Penna, Alois Fürst, Demetris Papamichael (+16 others)
2018 European Journal of Surgical Oncology  
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more » ... r the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal. If the publication is distributed under the terms of Article 25fa of the Dutch Copyright Act, indicated by the "Taverne" license above, please follow below link for the End User
doi:10.1016/j.ejso.2018.08.003 pmid:30150158 fatcat:k6ckhigmrbe4la2ck2mt7fmui4

Page 428 of Murray's Magazine Vol. 7, Issue 40 [page]

1890 Murray's Magazine  
Arthur Chappell). The programme now lies before me, and among the artists assisting were Madame Lemmens and Herr Henschel. That concert took place on June 28th, 1878, at the house of Mr.  ...  Arthur Balfour in Carlton Gardens, and under the patronage of H.R.H.  ... 

Page 242 of Musical World Vol. 42, Issue 16 [page]

1864 Musical World  
LEMMENS. KIRKMAN'S PIANOFORTE.  ...  The Lady Adeliza Manners, Mrs, Arthur Pott. The Lady Leigh. Mrs. Bishop Culpeper. The Lady Taunton. Mrs. Herbert Ingram. The Lady Bagot. Mrs. Beaumont, The Lady Jane Repton.  ... 

Page 143 of Musical World Vol. 44, Issue 9 [page]

1866 Musical World  
Lemmens Suereineton’s favorite Song. 3s, ARLY LOVE. F. Muscrave. 4th Edition. 4 2s. 6d. | oe hima BLUE SEA. ArtHur S§. SULLIVAN. ARTHUR S. Henry SMART. ONY A WITHERED ROSE. J. R.  ...  ArtHur S. SULLIVAN. Mr. Cumminas. 2s. 6d. \ Sung by SONG. ArtHour S. SULLIVAN. 6d. ILLOW For Contralto. 2s. MISTRESS MINE. Sung by Mr. Santtey. 2s. 6d. JIGH NO MORE, LADIES. Suntivan. Sung by Mr.  ... 

The 'St. Matthew' Passion in Spain

Arthur G. Colborn
1921 The Musical Times  
Arthur E. Sims, Central Hall, Newport-Marche Pontificale, Lemmens; March for a Church Festival, Best.  ...  lettcrs to the E itor 2, Park View, ARTHUR G. COLBORN. Stapleton, Bristol. March 8, 1921. [Below is an extract from the programme kindly sent by Mr.  ... 
doi:10.2307/910579 fatcat:6frtpanl4janrpzd6oigeqmgce

Page 171 of Musical World Vol. 42, Issue 11 [page]

1864 Musical World  
Arthur Chappell, the Manager, would have been induced still further to extend the series.  ...  Arthur Chappell’s quartet in ordinary (MM. Vieuxtemps, L. Ries, H. Webb and Paque), and on the whole, the finest performance of the evening.  ... 

Page 356 of The Academy and Literature Vol. 49, Issue 1252 [page]

1896 The Academy and Literature  
Poems by ARTHUR SYMONS. 500 Copies, printed at the Chiswick Press. Large post 8vo, cloth, 6s. net. Fifty Large-Paper — £1 Is. net. SILHOUETTES. By Arthur SYMONS. Second Edition.  ...  Lemmen, and 11 Drawings by Aubrey Beardsley. No. If. APRIL, 1896, NOW READY, upwards of 20 pages, 20 Full-page Illustrations. No.  ... 

Page 93 of Savoy 1896 Vol. , Issue 7 [page]

1896 Savoy 1896  
EDITED BY ARTHUR SYMONS. No. 1. JANUARY, 1896. 170 pages, 18 full-page Illustrations, and 5 Illustrations in the Text. No. I contains literary contributions by G.  ...  Lemmen, and Eleven Drawings by Aubrey Beardsley. Crown 4to, bound in pictorial cover, 2s. 6d. net. No. 2. APRIL, 1896. 202 pages, and 20 full-page Illustrations.  ... 

Page 94 of Savoy 1896 Vol. , Issue 8 [page]

1896 Savoy 1896  
EDITED BY ARTHUR SYMONS. No. 1. JANUARY, 1896. 170 pages, 18 full-page Illustrations, and 5 Illustrations in the Text. No. 1 contains literary contributions by G.  ...  Lemmen, and Eleven Drawings by Aubrey eardsley. Crown 4to, bound in pictorial cover, 2s. 6d. net. No. 2. APRIL, 1896. 202 pages, and 20 full-page Illustrations.  ... 

Page 98 of Musical World Vol. 44, Issue 7 [page]

1866 Musical World  
Made so popular by Madame Lemmens-Sherrington’s exquisite singing. 2s. 6d. IS THE MOONLIGHT SLEEPING.  ...  Lemmens-Suerrineron’s favorite Song. 3s. ERENA. Francesco BEerGer. Louisa Pyne. 3s. | anes LOVE. 2s. 6d. Artuur S. Sung by Miss F. Muscrave. 4th Edition. EARING OF THE Song. 2s. 6d.  ... 
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