How Valid Are Animal Models to Evaluate Treatments for Pulmonary Hypertension?

Overview

Journal Naunyn Schmiedebergs Arch Pharmacol

Specialty Pharmacology

Date 2006 Aug 26

PMID 16932922

Citations 27

Authors

Maria E Campian

Maxim Hardziyenka

Martin C Michel

Hanno L Tan

Affiliations

Soon will be listed here.

Abstract

Various animal models of pulmonary hypertension (PH) exist, among which injection of monocrotaline (MCT) and exposure to hypoxia are used most frequently. These animal models have not only been used to characterize the pathophysiology of PH and its sequelae such as right ventricular hypertrophy and failure, but also to test novel therapeutic strategies. This manuscript summarizes the available treatment studies in animal models of PH, and compares the findings to those obtained in patients with PH. The analysis shows that all approaches which have proven successful in patients, most notably prostacyclin and its analogs and endothelin receptor antagonists, are also effective in various animal models. However, the opposite it not always true. Therefore, promising results in animals have to be interpreted carefully until confirmed in clinical studies.

Citing Articles

Hypoxia modeling techniques: A review.

Salyha N, Oliynyk I Heliyon. 2023; 9(2):e13238.

PMID: 36718422 PMC: 9877323. DOI: 10.1016/j.heliyon.2023.e13238.

Farnesyl diphosphate synthase regulated endothelial proliferation and autophagy during rat pulmonary arterial hypertension induced by monocrotaline.

Jin T, Lu J, Lv Q, Gong Y, Feng Z, Ying H Mol Med. 2022; 28(1):94.

PMID: 35962329 PMC: 9373289. DOI: 10.1186/s10020-022-00511-7.

Plexiform Lesions in an Experimental Model of Monocrotalin-Induced Pulmonary Arterial Hypertension.

Gewehr D, Salgueiro G, de Noronha L, Kubrusly F, Kubrusly L, Coltro G Arq Bras Cardiol. 2020; 115(3):480-490.

PMID: 33027370 PMC: 9363102. DOI: 10.36660/abc.20190306.

Changes in heart morphometric parameters over the course of a monocrotaline-induced pulmonary arterial hypertension rat model.

Holda M, Szczepanek E, Bielawska J, Palka N, Wojtysiak D, Fraczek P J Transl Med. 2020; 18(1):262.

PMID: 32605656 PMC: 7325143. DOI: 10.1186/s12967-020-02440-7.

Association between a Single Nucleotide Polymorphism in the 3'-UTR of and the Risk of Nonidiopathic Pulmonary Arterial Hypertension in Chinese Population.

Li D, Sun Y, Kong X, Luan C, Yu Y, Chen F Dis Markers. 2018; 2018:2461845.

PMID: 30405854 PMC: 6204199. DOI: 10.1155/2018/2461845.

References

Meyrick B, Reid L . The effect of continued hypoxia on rat pulmonary arterial circulation. An ultrastructural study. Lab Invest. 1978; 38(2):188-200. View

Roberts Jr J, Chiche J, Weimann J, Steudel W, Zapol W, Bloch K . Nitric oxide inhalation decreases pulmonary artery remodeling in the injured lungs of rat pups. Circ Res. 2000; 87(2):140-5. DOI: 10.1161/01.res.87.2.140. View

Shelub I, van Grondelle A, McCullough R, Hofmeister S, Reeves J . A model of embolic chronic pulmonary hypertension in the dog. J Appl Physiol Respir Environ Exerc Physiol. 1984; 56(3):810-5. DOI: 10.1152/jappl.1984.56.3.810. View

Saji T, Ozawa Y, Ishikita T, Matsuura H, Matsuo N . Short-term hemodynamic effect of a new oral PGI2 analogue, beraprost, in primary and secondary pulmonary hypertension. Am J Cardiol. 1996; 78(2):244-7. DOI: 10.1016/s0002-9149(96)90408-7. View

Tantini B, Manes A, Fiumana E, Pignatti C, Guarnieri C, Zannoli R . Antiproliferative effect of sildenafil on human pulmonary artery smooth muscle cells. Basic Res Cardiol. 2005; 100(2):131-8. DOI: 10.1007/s00395-004-0504-5. View

Nguyen Q, Colombo F, Rouleau J, Dupuis J, Calderone A . LU135252, an endothelin(A) receptor antagonist did not prevent pulmonary vascular remodelling or lung fibrosis in a rat model of myocardial infarction. Br J Pharmacol. 2000; 130(7):1525-30. PMC: 1572223. DOI: 10.1038/sj.bjp.0703466. View

Kim H, Yung G, Marsh J, Konopka R, Pedersen C, Chiles P . Endothelin mediates pulmonary vascular remodelling in a canine model of chronic embolic pulmonary hypertension. Eur Respir J. 2000; 15(4):640-8. DOI: 10.1034/j.1399-3003.2000.15d04.x. View

Hill N, Warburton R, Pietras L, Klinger J . Nonspecific endothelin-receptor antagonist blunts monocrotaline-induced pulmonary hypertension in rats. J Appl Physiol (1985). 1997; 83(4):1209-15. DOI: 10.1152/jappl.1997.83.4.1209. View

Weitzenblum E, Chaouat A . Hypoxic pulmonary hypertension in man: what minimum daily duration of hypoxaemia is required?. Eur Respir J. 2001; 18(2):251-3. DOI: 10.1183/09031936.01.00242501. View

10.

Eddahibi S, Raffestin B, Clozel M, LEVAME M, Adnot S . Protection from pulmonary hypertension with an orally active endothelin receptor antagonist in hypoxic rats. Am J Physiol. 1995; 268(2 Pt 2):H828-35. DOI: 10.1152/ajpheart.1995.268.2.H828. View

11.

Miyata M, Ueno Y, Sekine H, Ito O, Sakuma F, Koike H . Protective effect of beraprost sodium, a stable prostacyclin analogue, in development of monocrotaline-induced pulmonary hypertension. J Cardiovasc Pharmacol. 1996; 27(1):20-6. DOI: 10.1097/00005344-199601000-00004. View

12.

Ueno M, Miyauchi T, Sakai S, Yamauchi-Kohno R, Goto K, Yamaguchi I . A combination of oral endothelin-A receptor antagonist and oral prostacyclin analogue is superior to each drug alone in ameliorating pulmonary hypertension in rats. J Am Coll Cardiol. 2002; 40(1):175-81. DOI: 10.1016/s0735-1097(02)01911-3. View

13.

Morel O, Buvry A, Le Corvoisier P, Tual L, Favret F, Leon-Velarde F . Effects of nifedipine-induced pulmonary vasodilatation on cardiac receptors and protein kinase C isoforms in the chronically hypoxic rat. Pflugers Arch. 2003; 446(3):356-64. DOI: 10.1007/s00424-003-1034-y. View

14.

Galie N, Ghofrani H, Torbicki A, Barst R, Rubin L, Badesch D . Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med. 2005; 353(20):2148-57. DOI: 10.1056/NEJMoa050010. View

15.

Belik J, Halayko A, Rao K, Stephens N . Fetal ductus arteriosus ligation. Pulmonary vascular smooth muscle biochemical and mechanical changes. Circ Res. 1993; 72(3):588-96. DOI: 10.1161/01.res.72.3.588. View

16.

Richalet J, Gratadour P, Robach P, Pham I, Dechaux M, Joncquiert-Latarjet A . Sildenafil inhibits altitude-induced hypoxemia and pulmonary hypertension. Am J Respir Crit Care Med. 2004; 171(3):275-81. DOI: 10.1164/rccm.200406-804OC. View

17.

Lopes A, Maeda N, Goncalves R, Bydlowski S . Endothelial cell dysfunction correlates differentially with survival in primary and secondary pulmonary hypertension. Am Heart J. 2000; 139(4):618-23. DOI: 10.1016/s0002-8703(00)90038-3. View

18.

Malik A, van der Zee H . Time course of pulmonary vascular response to microembolization. J Appl Physiol Respir Environ Exerc Physiol. 1977; 43(1):51-8. DOI: 10.1152/jappl.1977.43.1.51. View

19.

Voelkel N, Tuder R, Bridges J, Arend W . Interleukin-1 receptor antagonist treatment reduces pulmonary hypertension generated in rats by monocrotaline. Am J Respir Cell Mol Biol. 1994; 11(6):664-75. DOI: 10.1165/ajrcmb.11.6.7946395. View

20.

Kataoka M, Nagaya N, Satoh T, Itoh T, Murakami S, Iwase T . A long-acting prostacyclin agonist with thromboxane inhibitory activity for pulmonary hypertension. Am J Respir Crit Care Med. 2005; 172(12):1575-80. DOI: 10.1164/rccm.200501-102OC. View