Role of the endothelin system in secondary pulmonary hypertension related to air embolism: Lessons learned from testing four classes of endothelin blockers in a rat model

Journal of Cardiovascular Pharmacology

Volumn 44, Issue SUPPL. 1, 2004, Pages

  Battistini, B ^a,f   Verreault, M ^a   Ayach, B ^a   Blouin, A ^a   Cernacek, P ^b   Jeng, A Y ^g   Wessale, J ^c,d   Opgenorth, T ^c,d   Tsang, J ^e  

^a LAVAL UNIVERSITY   (Canada)

^b ROYAL VICTORIA HOSPITAL   (Canada)

^c NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

^d ABBOTT LABORATORIES   (United States)

^e UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^f LAVAL UNIVERSITY   (Canada)

^g NONE

Author keywords

Antagonists; Blood gas; Endothelin; Endothelin receptor; Endothelin converting enzyme; Inhibitors; Pulmonary air embolism; Pulmonary hypertension

Indexed keywords

(3 FLUORO 4 METHOXYPHENYL)(1,3 BENZODIOXOL 5 YL) 1 [2 [N (N PROPYL) N (N PENTYLSULFONYL)AMINO]ETHYL]PYRROLIDINE CARBOXYLIC ACID; 4 (1,3 BENZODIOXOL 5 YL) 1 [(2,6 DIETHYLPHENYL)CARBAMOYLMETHYL] 2 (4 PROPOXYPHENYL) 3 PYRROLIDINECARBOXYLIC ACID; A 182086; ALPHA [(PHOSPHONOMETHYL)AMINO]DIBENZOFURAN 3 PROPANOIC ACID; ATRASENTAN; CGS 35066; ENDOTHELIN; ENDOTHELIN A RECEPTOR ANTAGONIST; ENDOTHELIN B RECEPTOR ANTAGONIST; ENDOTHELIN CONVERTING ENZYME INHIBITOR; ENDOTHELIN RECEPTOR ANTAGONIST; OXYGEN; UNCLASSIFIED DRUG;

ACUTE DISEASE; AIR EMBOLISM; ANIMAL EXPERIMENT; ANIMAL MODEL; CONFERENCE PAPER; CONTROLLED STUDY; DRUG EFFECT; DRUG EFFICACY; DRUG SCREENING; DRUG SELECTIVITY; EVALUATION; HEART RATE; HEART RIGHT VENTRICLE; HEART RIGHT VENTRICLE PRESSURE; LUNG EMBOLISM; MALE; MEAN ARTERIAL PRESSURE; NONHUMAN; OXYGEN SATURATION; OXYGEN TENSION; PRIORITY JOURNAL; PULMONARY HYPERTENSION; RAT; SYSTOLIC BLOOD PRESSURE; TIME;

ACUTE DISEASE; ANIMALS; ASPARTIC ENDOPEPTIDASES; BENZOFURANS; CARDIOVASCULAR AGENTS; DISEASE MODELS, ANIMAL; EMBOLISM, AIR; ENDOTHELINS; HEMODYNAMICS; HYPERTENSION, PULMONARY; MALE; METALLOENDOPEPTIDASES; PHOSPHONIC ACIDS; PROTEASE INHIBITORS; PYRROLIDINES; RATS; RATS, SPRAGUE-DAWLEY; RECEPTOR, ENDOTHELIN A; RECEPTOR, ENDOTHELIN B; SULFONAMIDES; TIME FACTORS; VENTRICULAR DYSFUNCTION, RIGHT;

EID: 11144253601     PISSN: 01602446     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.fjc.0000166295.18066.f8     Document Type: Conference Paper

References (21)

1. Riedel M. Venous thromboembolic disease; acute pulmonary embolism 1: pathophysiology, clinical presentation, and diagnosis. Heart. 2001;1:229-240.
2. Smulders YM. Pathophysiology and treatment of haemodynamic instability in acute pulmonary embolism: the pivotal role of pulmonary vasoconstriction. Cardiovasc Res. 200;48:23-33.
3. Smulders YM. Contribution of pulmonary vasoconstriction to haemodynamic instability after acute pulmonary embolism. Implications for treatment? Neth J Med. 2001;58:241-247.
4. Battistini B. Modulation of the endothelins and roles of this novel humoral system in acute pulmonary embolism. Can J Physiol Pharmacol. 2003;81:555-569.
5. Battistini B, Dussault P. Blocking of the endothelin system: the development of receptor antagonists. Pulm Pharmacol Ther. 1998;11:97-112.
6. A receptor antagonist, ABT-627, in healthy normotensive anaesthetized rats developing acute pulmonary air embolism. Clin Sci (Lond). 2002;103:371-375.
7. B receptor antagonists in acute pulmonary air embolism in rats. Br J Pharmacol. 2004;in press.
8. Verreault M, Tsang J, Pheng LH, et al. Effects of a selective endothelin converting enzyme inhibitor, CGS 35066, in a rat model of acute pulmonary air embolism. J Pharmacol Exp Ther. 2004;submitted.
9. Winn M, von Geldern TW, Opgenorth TJ, et al. 2,4-Diarylpyrrolidine-3- carboxylic acids - potent ETA selective endothelin receptor antagonists. 1. Discovery of A-127722. J Med Chem. 1996;39:1039-1048.
10. Von Geldern TW, Tasker AS, Sorensen BK, et al. Pyrrolidine-3-carboxylic acids as endothelin antagonists. 4. Side chain conformational restriction leads to ET(B) selectivity. J Med Chem. 1998;42:3668-3678.
11. Wessale JL, Adler AL, Novosad EI, et al. Pharmacology of endothelin receptor antagonists ABT-627, ABT-546, A-182086 and A-192621: ex vivo and in vivo studies. Clin Sci (Lond). 2002;103(suppl 48):112S-117S.
12. Battistini B, Jeng, AY. Endothelin-converting enzyme inhibitors and their effects. Handbook Exp Pharmacol. 2001;152:155-208.
13. Sofia M, Faraone S, Alifano M, et al. Endothelin abnormalities in patients with pulmonary embolism. Chest. 1997;111:544-549.
14. Takahashi H, Soma S, Muramatsu M, et al. Upregulation of ET-1 and its receptors and remodeling in small pulmonary veins under hypoxic conditions. Am J Physiol Lung Cell Mol Physiol. 2001;280:L1104-L1114.
15. Bonvallet ST, Zamora MR, Hasunuma K, et al. BQ123, an ETA-receptor antagonist, attenuates hypoxic pulmonary hypertension in rats. Am J Physiol. 1994;266:H1327-H1331.
16. Chen SJ, Chen YF, Opgenorth TJ, et al. The orally active nonpeptide endothelin A-receptor antagonist A-127722 prevents and reverses hypoxia-induced pulmonary hypertension and pulmonary vascular remodeling in Sprague-Dawley rats. J Cardiovasc Pharmacol. 1997; 29:713-725.
17. Holm P, Liska J, Franco-Cereceda A. The ETA receptor antagonist, BMS-182874, reduces acute hypoxic pulmonary hypertension in pigs in vivo. Cardiovasc Res. 1998;37:765-771.
18. Hirata Y, Emori T, Eguchi S, et al. Endothelin receptor subtype B mediates synthesis of nitric oxide by cultured bovine endothelial cells. J Clin Invest. 1993;91:1367-1373.
19. McMurdo L, Lidbury PS, Thiemermann C, Vane JR. Mediation of endothelin-1-induced inhibition of platelet aggregation via the ETB receptor. Br J Pharmacol. 1993;109:530-534.
20. Fukuroda T, Fujikawa T, Ozaki S, et al. Clearance of circulating endothelin-1 by ETB receptors in rats. Biochem Biophys Res Commun. 1994;199:1461-1465.
21. Dupuis J, Goresky CA, Fournier A. Pulmonary clearance of circulating endothelin-1 in dogs in vivo: exclusive role of ETB receptors. J Appl Physiol. 1996;81:1510-1515.