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Ther.<\/i>, 26<\/b>, 813\u2013825 (2009).","DOI":"10.1007\/s12325-009-0064-z"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5) Barnes PJ. New therapies for chronic obstructive pulmonary disease. Med. Princ. Pract.<\/i>, 19<\/b>, 330\u2013338 (2010).","DOI":"10.1159\/000316368"},{"key":"6","unstructured":"6) Giembycz MA, Field SK. Roflumilast: first phosphodiesterase 4 inhibitor approved for treatment of COPD. Drug Des. Devel. Ther.<\/i>, 4<\/b>, 147\u2013158 (2010)."},{"key":"7","doi-asserted-by":"crossref","unstructured":"7) Mori H, Nose T, Ishitani K, Kasagi S, Souma S, Akiyoshi T, Kodama Y, Mori T, Kondo M, Sasaki S, Iwase A, Takahashi K, Fukuchi Y, Seyama K. Phosphodiesterase 4 inhibitor GPD-1116 markedly attenuates the development of cigarette smoke-induced emphysema in senescence-accelerated mice P1 strain. Am. J. Physiol. Lung Cell. Mol. 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Pharmacol.<\/i>, 46<\/b>, 833\u2013839 (1993).","DOI":"10.1016\/0006-2952(93)90492-F"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11) Corbel M, Germain N, Lanchou J, Molet S, R e Silva PM, Martins MA, Boichot E, Lagente V. The selective phosphodiesterase 4 inhibitor RP 73-401 reduced matrix metalloproteinase 9 activity and transforming growth factor-beta release during acute lung injury in mice: the role of the balance between tumor necrosis factor-alpha and interleukin-10. J. Pharmacol. Exp. Ther.<\/i>, 301<\/b>, 258\u2013265 (2002).","DOI":"10.1124\/jpet.301.1.258"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12) Ito A, Nose T, Takahashi S, Mori Y. Cyclooxygenase inhibitors augment the production of pro-matrix metalloproteinase 9 (progelatinase B) in rabbit articular chondrocytes. FEBS Lett.<\/i>, 360<\/b>, 75\u201379 (1995).","DOI":"10.1016\/0014-5793(95)00085-N"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13) Mizutani N, Fuchikami J, Takahashi M, Nabe T, Yoshino S, Kohno S. Pulmonary emphysema induced by cigarette smoke solution and lipopolysaccharide in guinea pigs. Biol. Pharm. Bull.<\/i>, 32<\/b>, 1559\u20131564 (2009).","DOI":"10.1248\/bpb.32.1559"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14) Izikki M, Raffestin B, Klar J, Hatzelmann A, Marx D, Tenor H, Zadigue P, Adnot S, Eddahibi S. Effects of roflumilast, a phosphodiesterase-4 inhibitor, on hypoxia- and monocrotaline-induced pulmonary hypertension in rats. J. Pharmacol. Exp. Ther.<\/i>, 330<\/b>, 54\u201362 (2009).","DOI":"10.1124\/jpet.108.148742"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15) Sawamura F, Kato M, Fujita K, Nakazawa T, Beardsworth A. Tadalafil, a long-acting inhibitor of PDE5, improves pulmonary hemodynamics and survival rate of monocrotaline-induced pulmonary artery hypertension in rats. J. Pharmacol. Sci.<\/i>, 111<\/b>, 235\u2013243 (2009).","DOI":"10.1254\/jphs.09110FP"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16) Wang YJ, Jiang YL, Tang HF, Zhao CZ, Chen JQ. Zl-n<\/i>-91, a selective phosphodiesterase 4 inhibitor, suppresses inflammatory response in a COPD-like rat model. Int. Immunopharmacol.<\/i>, 10<\/b>, 252\u2013258 (2010).","DOI":"10.1016\/j.intimp.2009.11.008"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17) McCluskie K, Klein U, Linnevers C, Ji YH, Yang A, Husfeld C, Thomas GR. Phosphodiesterase type 4 inhibitors cause proinflammatory effects in vivo.<\/i> J. Pharmacol. Exp. Ther.<\/i>, 319<\/b>, 468\u2013476 (2006).","DOI":"10.1124\/jpet.106.105080"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18) Bundschuh DS, Eltze M, Barsig J, Wollin L, Hatzelmann A, Beume R. In vivo<\/i> efficacy in airway disease models of roflumilast, a novel orally active PDE4 inhibitor. J. Pharmacol. Exp. Ther.<\/i>, 297<\/b>, 280\u2013290 (2001).","DOI":"10.1016\/S0022-3565(24)29538-0"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19) Kubo S, Kobayashi M, Iwata M, Miyata K, Takahashi K, Shimizu Y. Anti-neutrophilic inflammatory activity of ASP3258, a novel phosphodiesterase type 4 inhibitor. Int. Immunopharmacol.<\/i>, 12<\/b>, 59\u201363 (2012).","DOI":"10.1016\/j.intimp.2011.10.011"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20) Gibson LC, Hastings SF, McPhee I, Clayton RA, Darroch CE, Mackenzie A, Mackenzie FL, Nagasawa M, Stevens PA, Mackenzie SJ. The inhibitory profile of Ibudilast against the human phosphodiesterase enzyme family. Eur. J. Pharmacol.<\/i>, 538<\/b>, 39\u201342 (2006).","DOI":"10.1016\/j.ejphar.2006.02.053"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21) Manabe H, Akuta K, Sejimo H, Kawasaki H, Nukui E, Ichimura M, Kase H, Kawakita T, Suzuki F, Kitamura S, Sato S, Ohmori K. Anti-inflammatory and bronchodilator properties of KF19514, a phosphodiesterase 4 and 1 inhibitor. Eur. J. Pharmacol.<\/i>, 332<\/b>, 97\u2013107 (1997).","DOI":"10.1016\/S0014-2999(97)01063-7"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22) Hatzelmann A, Schudt C. Anti-inflammatory and immunomodulatory potential of the novel PDE4 inhibitor roflumilast in vitro.<\/i> J. Pharmacol. Exp. Ther.<\/i>, 297<\/b>, 267\u2013279 (2001).","DOI":"10.1016\/S0022-3565(24)29537-9"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23) Serezani CH, Ballinger MN, Aronoff DM, Peters-Golden M. Cyclic AMP: master regulator of innate immune cell function. Am. J. Respir. Cell Mol. 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Care Med.<\/i>, 158<\/b> (Suppl. 2), S146\u2013S153 (1998).","DOI":"10.1164\/ajrccm.158.supplement_2.13tac110"},{"key":"28","doi-asserted-by":"crossref","unstructured":"28) Cazzola M, Calzetta L, Matera MG. \u03b22-Adrenoceptor agonists: current and future direction. Br. J. Pharmacol.<\/i>, 163<\/b>, 4\u201317 (2011).","DOI":"10.1111\/j.1476-5381.2011.01216.x"},{"key":"29","doi-asserted-by":"crossref","unstructured":"29) Takimoto E. Cyclic GMP-dependent signaling in cardiac myocytes. Circ. J.<\/i>, 76<\/b>, 1819\u20131825 (2012).","DOI":"10.1253\/circj.CJ-12-0664"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30) Russwurm M, Russwurm C, Koesling D, Mergia E. NO\/cGMP: the past, the present, and the future. Methods Mol. Biol.<\/i>, 1020<\/b>, 1\u201316 (2013).","DOI":"10.1007\/978-1-62703-459-3_1"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31) Zhihui Q. Modulating nitric oxide signaling in the CNS for Alzheimer\u2019s disease therapy. Future Med. Chem.<\/i>, 5<\/b>, 1451\u20131468 (2013).","DOI":"10.4155\/fmc.13.111"},{"key":"32","doi-asserted-by":"crossref","unstructured":"32) Abrams J. Beneficial actions of nitrates in cardiovascular disease. Am. J. Cardiol.<\/i>, 77<\/b>, C31\u2013C37 (1996).","DOI":"10.1016\/S0002-9149(96)00186-5"},{"key":"33","doi-asserted-by":"crossref","unstructured":"33) Murray F, Patel HH, Suda RYS, Zhang S, Thistlethwaite PA, Yuan X-J, Insel PA. Expression and activity of cAMP phosphodiesterase isoforms in pulmonary artery smooth muscle cells from patients with pulmonary hypertension: role for PDE1. Am. J. Physiol. Lung Cell. Mol. Physiol.<\/i>, 292<\/b>, L294\u2013L303 (2007).","DOI":"10.1152\/ajplung.00190.2006"},{"key":"34","doi-asserted-by":"crossref","unstructured":"34) Schermuly RT, Pullamsetti SS, Kwapiszewska G, Dumitrascu R, Tian X, Weissmann N, Ghofrani HA, Kaulen C, Dunkern T, Schudt C, Voswinckel R, Zhou J, Samidurai A, Klepetko W, Paddenberg R, Kummer W, Seeger W, Grimminger F. Phosphodiesterase 1 upregulation in pulmonary arterial hypertension: target for reverse-remodeling therapy. Circulation<\/i>, 115<\/b>, 2331\u20132339 (2007).","DOI":"10.1161\/CIRCULATIONAHA.106.676809"},{"key":"35","doi-asserted-by":"crossref","unstructured":"35) Chan S, Yan C. PDE1 isozymes, key regulators of pathological vascular remodeling. Curr. Opin. Pharmacol.<\/i>, 11<\/b>, 720\u2013724 (2011).","DOI":"10.1016\/j.coph.2011.09.002"},{"key":"36","doi-asserted-by":"crossref","unstructured":"36) Jeon KI, Jono H, Miller CL, Cai Y, Lim S, Liu X, Gao P, Abe J, Li JD, Yan C. Ca2+<\/sup>\/calmodulin-stimulated PDE1 regulates the beta-catenin\/TCF signaling through PP2A B56 gamma subunit in proliferating vascular smooth muscle cells. FEBS J.<\/i>, 277<\/b>, 5026\u20135039 (2010).","DOI":"10.1111\/j.1742-4658.2010.07908.x"},{"key":"37","doi-asserted-by":"crossref","unstructured":"37) Cai Y, Knight WE, Guo S, Li JD, Knight PA, Yan C. Vinpocetine suppresses pathological vascular remodeling by inhibiting vascular smooth muscle cell proliferation and migration. J. Pharmacol. Exp. Ther.<\/i>, 343<\/b>, 479\u2013488 (2012).","DOI":"10.1124\/jpet.112.195446"},{"key":"38","doi-asserted-by":"crossref","unstructured":"38) Nagel DJ, Aizawa T, Jeon KI, Liu W, Mohan A, Wei H, Miano JM, Florio VA, Gao P, Korshunov VA, Berk BC, Yan C. Role of nuclear Ca2+<\/sup>\/calmodulin-stimulated phosphodiesterase 1A in vascular smooth muscle cell growth and survival. Circ. Res.<\/i>, 98<\/b>, 777\u2013784 (2006).","DOI":"10.1161\/01.RES.0000215576.27615.fd"},{"key":"39","doi-asserted-by":"crossref","unstructured":"39) Suzuki O, Mizukami K, Etori M, Sogawa Y, Takagi N, Tsuchida H, Morimoto K, Goto T, Yoshino T, Mikkaichi T, Hirahara K, Nakamura S, Maeda H. Evaluation of the therapeutic index of a novel phosphodiesterase 4B-selective inhibitor over phosphodiesterase 4D in mice. J. Pharmacol. Sci.<\/i>, 123<\/b>, 219\u2013226 (2013).","DOI":"10.1254\/jphs.13103FP"},{"key":"40","unstructured":"40) Barnette MS, Christensen SB, Essayan DM, Grous M, Prabhakar U, Rush JA, Kagey-Sobotka A, Torphy TJ. SB 207499 (Ariflo), a potent and selective second-generation phosphodiesterase 4 inhibitor: in vitro<\/i> anti-inflammatory actions. J. Pharmacol. Exp. Ther.<\/i>, 284<\/b>, 420\u2013426 (1998)."},{"key":"41","unstructured":"41) Matsushita N, Shibazaki Y, Kawamata S, Ohnishi M, Nakayoshi T, Shizuki S, Iizuka H, Hirata M, Unakami S. General pharmacological properties of rolipram. 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