Imatinib attenuates monocrotaline pulmonary hypertension and has potent vasodilator activity in pulmonary and systemic vascular beds in the rat

American Journal of Physiology - Heart and Circulatory Physiology

Volumn 305, Issue 9, 2013, Pages

  Pankey, Edward A ^a   Thammasiboon, Supat ^a   Lasker, George F ^a   Baber, Syed ^a   Lasky, Joseph A ^a   Kadowitz, Philip J ^a  

^a TULANE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Imatinib; PDGF; Pulmonary vascular bed; Tyrosine kinase inhibitor; Vasodilation

Indexed keywords

15 HYDROXY 11ALPHA,9ALPHA EPOXYMETHANOPROSTA 5,13 DIENOIC ACID; ADENOSINE TRIPHOSPHATE SENSITIVE POTASSIUM CHANNEL; CYCLIC AMP; FASUDIL; GLIBENCLAMIDE; IMATINIB; ISRADIPINE; MECLOFENAMIC ACID; MONOCROTALINE; N(G) NITROARGININE METHYL ESTER; PLATELET DERIVED GROWTH FACTOR; PLATELET DERIVED GROWTH FACTOR RECEPTOR; PROSTAGLANDIN SYNTHASE; ROLIPRAM;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTERIAL PRESSURE; ARTICLE; CONTROLLED STUDY; DNA SYNTHESIS; DOSE RESPONSE; HEART OUTPUT; HEART RIGHT VENTRICLE HYPERTROPHY; LUNG ARTERY PRESSURE; MALE; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; PULMONARY ARTERY; PULMONARY HYPERTENSION; RAT; SMOOTH MUSCLE FIBER; TREATMENT RESPONSE;

IMATINIB; PDGF; PULMONARY VASCULAR BED; TYROSINE KINASE INHIBITOR; VASODILATION;

ANIMALS; ANTIHYPERTENSIVE AGENTS; ARTERIAL PRESSURE; BENZAMIDES; CYCLOOXYGENASE INHIBITORS; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; HYPERTENSION, PULMONARY; HYPERTROPHY, RIGHT VENTRICULAR; MALE; MONOCROTALINE; MUSCLE, SMOOTH, VASCULAR; PHOSPHODIESTERASE 4 INHIBITORS; PIPERAZINES; POTASSIUM CHANNEL BLOCKERS; PROTEIN KINASE INHIBITORS; PULMONARY ARTERY; PYRIMIDINES; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, PLATELET-DERIVED GROWTH FACTOR; VASOCONSTRICTION; VASODILATION; VASODILATOR AGENTS;

EID: 84886992495     PISSN: 03636135     EISSN: 15221539     Source Type: Journal    
DOI: 10.1152/ajpheart.00329.2013     Document Type: Article

References (33)

1. Abe K, Toba M, Alzoubi A, Koubsky K, Ito M, Ota H, Gairhe S, Gerthoffer WT, Fagan KA, McMurtry IF, Oka M. Tyrosine kinase inhibitors are potent acute pulmonary vasodilators in rats. Am J Respir Cell Mol Biol 45: 804-808, 2011.
2. Badejo AM Jr, Dhaliwal JS, Casey DB, Gallen TB, Greco AJ, Kadowitz PJ. Analysis of pulmonary vasodilator responses to the Rho-kinase inhibitor fasudil in the anesthetized rat. Am J Physiol Lung Cell Mol Physiol 295: L828-L836, 2008.
3. Berk BC, Brock TA, Webb RC, Taubman MB, Atkinson WJ, Gimbrone MA Jr, Alexander RW. Epidermal growth factor, a vascular smooth muscle mitogen, induces rat aortic contraction. J Clin Invest 75: 1083-1086, 1985.
4. Biers SM, Reynard JM, Doore T, Brading AF. The functional effects of a c-kit tyrosine inhibitor on guinea-pig and human detrusor. BJU Int 97: 612-616, 2006.
5. Carroll M, Ohno-Jones S, Tamura S, Buchdunger E, Zimmermann J, Lydon NB, Gilliland DG, Druker BJ. CGP 57148, a tyrosine kinase inhibitor, inhibits the growth of cells expressing BCR-ABL, TEL-ABL, and TEL-PDGFR fusion proteins. Blood 90: 4947-4952, 1997.
6. Chattergoon NN, D'Souza FM, Deng W, Chen H, Hyman AL, Kadowitz PJ, Jeter JR Jr. Antiproliferative effects of calcitonin gene-related peptide in aortic and pulmonary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 288: L202-L211, 2005.
7. Cretoiu SM, Simionescu AA, Caravia L, Curici A, Cretoiu D, Popescu LM. Complex effects of imatinib on spontaneous and oxytocin-induced contractions in human non-pregnant myometrium. Acta Physiol Hung 98: 329-338, 2011.
8. Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S, Zimmermann J, Lydon NB. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med 2: 561-566, 1996.
9. Eriksson A, Nister M, Leveen P, Westermark B, Heldin CH, Claesson-Welsh L. Induction of platelet-derived growth factor alpha-and betareceptor mRNA and protein by platelet-derived growth factor BB. J Biol Chem 266: 21138-21144, 1991.
10. Ghofrani HA, Morrell NW, Hoeper MM, Olschewski H, Peacock AJ, Barst RJ, Shapiro S, Golpon H, Toshner M, Grimminger F, Pascoe S. Imatinib in pulmonary arterial hypertension patients with inadequate response to established therapy. Am J Respir Crit Care Med 182: 1171-1177, 2010.
11. Ghofrani HA, Seeger W, Grimminger F. Imatinib for the treatment of pulmonary arterial hypertension. N Engl J Med 353: 1412-1413, 2005.
12. Gur S, Kadowitz PJ, Hellstrom WJ. A protein tyrosine kinase inhibitor, imatinib mesylate (Gleevec), improves erectile and vascular function secondary to a reduction of hyperglycemia in diabetic rats. J Sex Med 7: 3341-3350, 2010.
13. Gur S, Sikka SC, Abdel-Mageed AB, Abd Elmageed ZY, Rezk B, Pankey E, Kadowitz PJ, Hellstrom WJ. Imatinib mesylate (Gleevec) induces human corpus cavernosum relaxation by inhibiting receptor tyrosine kinases (RTKs): identification of new RTK targets. Urology 82: 745. e11-745. e16, 2013.
14. Heldin CH, Westermark B. Mechanism of action and in vivo role of platelet-derived growth factor. Physiol Rev 79: 1283-1316, 1999.
15. Hoeper MM, Barst RJ, Bourge RC, Feldman J, Frost AE, Galie N, Gomez-Sanchez MA, Grimminger F, Grunig E, Hassoun PM, Morrell NW, Peacock AJ, Satoh T, Simonneau G, Tapson VF, Torres F, Lawrence D, Quinn DA, Ghofrani HA. Imatinib mesylate as add-on therapy for pulmonary arterial hypertension: results of the randomized IMPRES study. Circulation 127: 1128-1138, 2013.
16. Hubbard SR, Miller WT. Receptor tyrosine kinases: mechanisms of activation and signaling. Curr Opin Cell Biol 19: 117-123, 2007.
17. 2+ in rabbit isolated ear artery by platelet-derived growth factor. Br J Pharmacol 114: 138-142, 1995.
18. Hutchings G, Deprest J, Nilius B, Roskams T, De Ridder D. The effect of imatinib mesylate on the contractility of isolated rabbit myometrial strips. Gynecol Obstet Invest 62: 79-83, 2006.
19. Manley PW, Stiefl N, Cowan-Jacob SW, Kaufman S, Mestan J, Wartmann M, Wiesmann M, Woodman R, Gallagher N. Structural resemblances and comparisons of the relative pharmacological properties of imatinib and nilotinib. Bioorg Med Chem 18: 6977-6986, 2010.
20. McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, Rubin LJ, Tapson VF, Varga J. ACCF/AHA 2009 expert consensus document on pulmonary hypertension: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: developed in collaboration with the American College of Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension Association. J Am Coll Cardiol 53: 1573-1619, 2009.
21. Meyrick B, Reid L. Hypoxia-induced structural changes in the media and adventitia of the rat hilar pulmonary artery and their regression. Am J Pathol 100: 151-178, 1980.
22. Min Y, He P, Wang Q, Jin X, Song B, Li L. The effects of the c-kit blocker Glivec on the contractile response of urinary bladder. J Surg Res 171: e193-e199, 2011.
23. Ozgur-Akdemir A, Demirturk K, Karabakan M, Volkan-Oztekin C, Abdulkadir NA, Cetinkaya M, Gur S, Hellstrom WJ. Imatinib mesylate (Gleevec) as protein-tyrosine kinase inhibitor elicits smooth muscle relaxation in isolated human prostatic tissue. Urology 78: 968. e961-968. e966, 2011.
24. Pankey EA, Bhartiya M, Badejo AM Jr, Haider U, Stasch JP, Murthy SN, Nossaman BD, Kadowitz PJ. Pulmonary and systemic vasodilator responses to the soluble guanylyl cyclase activator, BAY 60-2770, are not dependent on endogenous nitric oxide or reduced heme. Am J Physiol Heart Circ Physiol 300: H792-H802, 2011.
25. Pankey EA, Lasker GF, Gur S, Hellstrom WJ, Kadowitz PJ. Analysis of erectile responses to imatinib in the rat. Urology 82: 253. e217-253. e224, 2013.
26. Popescu LM, Vidulescu C, Curici A, Caravia L, Simionescu AA, Ciontea SM, Simion S. Imatinib inhibits spontaneous rhythmic contractions of human uterus and intestine. Eur J Pharmacol 546: 177-181, 2006.
27. Rabinovitch M, Gamble W, Nadas AS, Miettinen OS, Reid L. Rat pulmonary circulation after chronic hypoxia: hemodynamic and structural features. Am J Physiol Heart Circ Physiol 236: H818-H827, 1979.
28. Rabinovitch M, Konstam MA, Gamble WJ, Papanicolaou N, Aronovitz MJ, Treves S, Reid L. Changes in pulmonary blood flow affect vascular response to chronic hypoxia in rats. Circ Res 52: 432-441, 1983.
29. Schermuly RT, Dony E, Ghofrani HA, Pullamsetti S, Savai R, Roth M, Sydykov A, Lai YJ, Weissmann N, Seeger W, Grimminger F. Reversal of experimental pulmonary hypertension by PDGF inhibition. J Clin Invest 115: 2811-2821, 2005.
30. Schiffer CA. BCR-ABL tyrosine kinase inhibitors for chronic myelogenous leukemia. N Engl J Med 357: 258-265, 2007.
31. Villalba N, Kun A, Stankevicius E, Simonsen U. Role for tyrosine kinases in contraction of rat penile small arteries. J Sex Med 7: 2086-2095, 2010.
32. Wang LD, Qiu XQ, Tian ZF, Zhang YF, Li HF. Inhibitory effects of genistein and resveratrol on guinea pig gallbladder contractility in vitro. World J Gastroenterol 14: 4955-4960, 2008.
33. Yamawaki H, Sato K, Hori M, Ozaki H, Nakamura S, Nakayama H, Doi K, Karaki H. Impairment of EDR by a long-term PDGF treatment in organ-cultured rabbit mesenteric artery. Am J Physiol Heart Circ Physiol 277: H318-H323, 1999.