Skip to main content
PMC home page
Thorax logoLink to Thorax
. 1982 Feb;37(2):88–96. doi: 10.1136/thx.37.2.88

Angiotensin converting enzyme activity and evolution of pulmonary vascular disease in rats with monocrotaline pulmonary hypertension.

J M Kay, P M Keane, K L Suyama, D Gauthier
PMCID: PMC459256  PMID: 6281933

Abstract

We have investigated the role of angiotensin converting enzyme (ACE) in the development of pulmonary hypertension, right ventricular hypertrophy, and pulmonary vascular disease in rats given a single subcutaneous injection of the pyrrolizidine alkaloid monocrotaline. Thirty-six young female Wistar rats were divided into a test group of 27 animals and a control group of nine animals. Each test rat was given a single subcutaneous injection of monocrotaline (60 mg/kg body weight). On the first, third, fifth, seventh, tenth, twelfth, fourteenth, seventeenth, and twenty-second days after the injection of monocrotaline the mean right ventricular systolic blood pressure was measured in one control and three test rats. The animals were then killed and we measured the specific activity of ACE in serum and lung homogenate. We also evaluated muscularisation of pulmonary arterioles, medial hypertrophy of muscular pulmonary arteries, and right ventricular hypertrophy. The sequence of changes was as follows: muscularisation of pulmonary arterioles and medial hypertrophy of muscular pulmonary arteries were apparent seven days after administration of monocrotaline; pulmonary hypertension and reduced lung ACE activity occurred after 10 days; right ventricular hypertrophy was detected after 12 days. Serum ACE activity was unchanged. It is concluded that the reduction in lung ACE activity is a result rather than a cause of the pulmonary hypertension. This reduction in lung ACE activity may be a protective mechanism designed to limit the elevation of the pulmonary arterial pressure.

Full text

PDF
95

Images in this article

89Image
on p.89
90Image
on p.90
90Image
on p.90
92Image
on p.92
93Image
on p.93

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abraham A. S., Kay J. M., Cole R. B., Pincock A. C. Haemodynamic and pathological study of the effect of chronic hypoxia and subsequent recovery of the heart and pulmonary vasculature of the rat. Cardiovasc Res. 1971 Jan;5(1):95–102. doi: 10.1093/cvr/5.1.95. [DOI] [PubMed] [Google Scholar]
  2. Caldwell P. R., Seegal B. C., Hsu K. C., Das M., Soffer R. L. Angiotensin-converting enzyme: vascular endothelial localization. Science. 1976 Mar 12;191(4231):1050–1051. doi: 10.1126/science.175444. [DOI] [PubMed] [Google Scholar]
  3. Carrillo L., Aviado D. M. Monocrotaline-induced pulmonary hypertension and p-chlorophenylalanine (PCPA). Lab Invest. 1969 Mar;20(3):243–248. [PubMed] [Google Scholar]
  4. Chesney C. F., Allen J. R., Hsu I. C. Right ventricular hypertrophy in monocrotaline pyrrole treated rats. Exp Mol Pathol. 1974 Apr;20(2):257–268. doi: 10.1016/0014-4800(74)90058-6. [DOI] [PubMed] [Google Scholar]
  5. Cushman D. W., Cheung H. S. Spectrophotometric assay and properties of the angiotensin-converting enzyme of rabbit lung. Biochem Pharmacol. 1971 Jul;20(7):1637–1648. doi: 10.1016/0006-2952(71)90292-9. [DOI] [PubMed] [Google Scholar]
  6. Erdös E. G. Angiotensin I converting enzyme. Circ Res. 1975 Feb;36(2):247–255. doi: 10.1161/01.res.36.2.247. [DOI] [PubMed] [Google Scholar]
  7. Hayashi Y., Hussa J. F., Lalich J. J. Cor pulmonale in rats. Lab Invest. 1967 Jun;16(6):875–881. [PubMed] [Google Scholar]
  8. Hollinger M. A., Giri S. N., Patwell S., Zuckerman J. E., Gorin A., Parsons G. Effect of acute lung injury on angiotensin converting enzyme in serum, lung lavage, and effusate. Am Rev Respir Dis. 1980 Feb;121(2):373–376. doi: 10.1164/arrd.1980.121.2.373. [DOI] [PubMed] [Google Scholar]
  9. Hollinger M. A., Patwell S. W., Zuckerman J. E., Gorin A. B., Parsons G., Giri S. N. Effect of paraquat on serum angiotensin converting enzyme. Am Rev Respir Dis. 1980 May;121(5):795–798. doi: 10.1164/arrd.1980.121.5.795. [DOI] [PubMed] [Google Scholar]
  10. Hunter C., Barer G. R., Shaw J. W., Clegg E. J. Growth of the heart and lungs in hypoxic rodents: a model of human hypoxic disease. Clin Sci Mol Med. 1974 Mar;46(3):375–391. doi: 10.1042/cs0460375. [DOI] [PubMed] [Google Scholar]
  11. Huxtable R., Ciaramitaro D., Eisenstein D. The effect of a pyrrolizidine alkaloid, monocrotaline, and a pyrrole, dehydroretronecine, on the biochemical functions of the pulmonary endothelium. Mol Pharmacol. 1978 Nov;14(6):1189–1203. [PubMed] [Google Scholar]
  12. Kay J. M., Gillund T. D., Heath D. Mast cells in the lungs of rats fed on Crotalaria spectabilis seeds. Am J Pathol. 1967 Dec;51(6):1031–1044. [PMC free article] [PubMed] [Google Scholar]
  13. Kay J. M., Heath D. Observations on the pulmonary arteries and heart weight of rats fed on Crotalaria spectabilis seeds. J Pathol Bacteriol. 1966 Oct;92(2):385–394. doi: 10.1002/path.1700920216. [DOI] [PubMed] [Google Scholar]
  14. Kay J. M., Smith P., Heath D. Electron microscopy of Crotalaria pulmonary hypertension. Thorax. 1969 Sep;24(5):511–526. doi: 10.1136/thx.24.5.511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kay J. M., Smith P., Heath D., Will J. A. Effects of phenobarbitone, cinnarizine, and zoxazolamine on the development of right ventricular hypertrophy and hypertensive pulmonary vascular disease in rats treated with monocrotaline. Cardiovasc Res. 1976 Mar;10(2):200–205. doi: 10.1093/cvr/10.2.200. [DOI] [PubMed] [Google Scholar]
  16. LENDRUM A. C., FRASER D. S., SLIDDERS W., HENDERSON R. Studies on the character and staining of fibrin. J Clin Pathol. 1962 Sep;15:401–413. doi: 10.1136/jcp.15.5.401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Le Treut A., Couliou H., Delbary M., Larzul J. J., De Labarthe B., Le Gall J. Y. Le dosage de l'enzyme de conversion de l'angiotensine I par méthode spectrophotométrique. Clin Chim Acta. 1979 Oct 15;98(1-2):1–4. doi: 10.1016/0009-8981(79)90158-x. [DOI] [PubMed] [Google Scholar]
  18. Leuenberger P. J., Stalcup S. A., Mellins R. B., Greenbaum L. M., Turino G. M. Decrease in angiotensin I conversion by acute hypoxia in dogs. Proc Soc Exp Biol Med. 1978 Sep;158(4):586–589. doi: 10.3181/00379727-158-40252. [DOI] [PubMed] [Google Scholar]
  19. Lieberman J. Elevation of serum angiotensin-converting-enzyme (ACE) level in sarcoidosis. Am J Med. 1975 Sep;59(3):365–372. doi: 10.1016/0002-9343(75)90395-2. [DOI] [PubMed] [Google Scholar]
  20. Mattocks A. R. Toxicity of pyrrolizidine alkaloids. Nature. 1968 Feb 24;217(5130):723–728. doi: 10.1038/217723a0. [DOI] [PubMed] [Google Scholar]
  21. Meijers C. A., Rutten J. C. A simple rapid method for the determination of total nitrogen in urine. Clin Chim Acta. 1969 May;24(2):308–310. doi: 10.1016/0009-8981(69)90329-5. [DOI] [PubMed] [Google Scholar]
  22. Meyrick B., Gamble W., Reid L. Development of Crotalaria pulmonary hypertension: hemodynamic and structural study. Am J Physiol. 1980 Nov;239(5):H692–H702. doi: 10.1152/ajpheart.1980.239.5.H692. [DOI] [PubMed] [Google Scholar]
  23. Miller P. J. An elastin stain. Med Lab Technol. 1971 Apr;28(2):148–149. [PubMed] [Google Scholar]
  24. Ng K. K., Vane J. R. Conversion of angiotensin I to angiotensin II. Nature. 1967 Nov 25;216(5117):762–766. doi: 10.1038/216762a0. [DOI] [PubMed] [Google Scholar]
  25. Oparil S., Low J., Koerner T. J. Altered angiotensin I conversion in pulmonary disease. Clin Sci Mol Med. 1976 Dec;51(6):537–543. doi: 10.1042/cs0510537. [DOI] [PubMed] [Google Scholar]
  26. Polsky-Cynkin R., Reichlin S., Fanburg B. L. Angiotensin-1-converting enzyme activity in the spontaneously hypertensive rat. Proc Soc Exp Biol Med. 1980 Jul;164(3):242–247. doi: 10.3181/00379727-164-40855. [DOI] [PubMed] [Google Scholar]
  27. Ryan J. W., Ryan U. S., Schultz D. R., Whitaker C., Chung A. Subcellular localization of pulmonary antiotensin-converting enzyme (kininase II). Biochem J. 1975 Feb;146(2):497–499. doi: 10.1042/bj1460497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. TAKEOKA O., ANGEVINE D. M., LALICH J. J. Stimulation of mast cells in rats fed various chemicals. Am J Pathol. 1962 May;40:545–554. [PMC free article] [PubMed] [Google Scholar]
  29. Valdivia E., Lalich J. J., Hayashi Y., Sonnad J. Alterations in pulmonary alveoli after a single injection of monocrotaline. Arch Pathol. 1967 Jul;84(1):64–76. [PubMed] [Google Scholar]
  30. Wagenvoort C. A., Wagenvoort N., Dijk H. J. Effect of fulvine on pulmonary arteries and veins of the rat. Thorax. 1974 Sep;29(5):522–529. doi: 10.1136/thx.29.5.522. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES