SC-39026, a serine elastase inhibitor, prevents muscularization of peripheral arteries, suggesting a mechanism of monocrotaline-induced pulmonary hypertension in rats

Circulation Research
R IlkiwM Rabinovitch

Abstract

In rats injected with the toxin monocrotaline, altered synthesis and distribution of pulmonary artery elastin suggest that increased elastase activity may be important in the development of vascular changes and progressive pulmonary hypertension. To test this hypothesis, male Sprague-Dawley rats (250-300 g) were given 40 mg/kg of the elastase inhibitor SC-39026 in a carboxymethylcellulose vehicle or vehicle only by gavage, 12 hours before and twice daily for 8 days after a single subcutaneous injection of either monocrotaline (60 mg/kg) or saline. Thirteen days after injection, indwelling cardiovascular catheters were inserted under pentobarbital anesthesia, and at 15 days after injection, pulmonary and systemic hemodynamic measurements were recorded with the animals awake. At post-mortem examination, the lungs were perfused and morphometric techniques applied for light and electron microscopic evaluation. Saline-injected rats given either SC-39026 or vehicle were similar in all features assessed. In contrast, monocrotaline-injected rats given SC-39026 had significantly lower mean pulmonary artery pressure than those given vehicle (21.0 +/- 1.6 vs. 27.5 +/- 0.8 mm Hg, p less than 0.05), and this correlated with a significant re...Continue Reading

References

Jan 1, 1979·The Anatomical Record·B Meyrick, L Reid
Oct 1, 1985·Proceedings of the Society for Experimental Biology and Medicine·A MolteniM Dunne
Mar 1, 1986·The Journal of Clinical Investigation·E KorneckiR H Lenox
Feb 1, 1986·Journal of Applied Physiology·G T CzerK M Moser
Sep 15, 1987·Biochemical and Biophysical Research Communications·A NakaoR A Mueller
Feb 1, 1987·Journal of Applied Physiology·K R StenmarkJ T Reeves
Oct 1, 1986·Experimental and Molecular Pathology·B FarisC Franzblau
Jul 1, 1986·Seminars in Thrombosis and Hemostasis·H L JamesA B Cohen
Dec 1, 1984·Collagen and Related Research·M S HibbsC L Mainardi
May 1, 1984·Proceedings of the Society for Experimental Biology and Medicine·A MolteniN H Solliday
Nov 1, 1983·Experimental Lung Research·T SugitaJ T Reeves
Feb 1, 1981·The American Journal of Physiology·F Ghodsi, J A Will
Dec 1, 1984·Journal of Applied Physiology: Respiratory, Environmental and Exercise Physiology·J S KerrH M Frankel
Aug 1, 1960·Proceedings of the Society for Experimental Biology and Medicine·J R WEEKS, J A JONES
Jul 1, 1952·British Heart Journal·R M FULTONA M JONES

❮ Previous
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Citations

Jan 1, 1990·Pharmacology & Therapeutics·R J Huxtable
Dec 26, 2001·Pharmacology & Therapeutics·T K Jeffery, J C Wanstall
May 19, 1994·The New England Journal of Medicine·G H Gibbons, V J Dzau
Jul 8, 2010·Circulation Journal : Official Journal of the Japanese Circulation Society·Erquan ZhangKazuo Maruyama
Jun 2, 2015·American Journal of Respiratory and Critical Care Medicine·Hyung J Chun, Paul B Yu
Sep 15, 2018·Annual Review of Medicine·Edda SpiekerkoetterVinicio A de Jesus Perez
Nov 28, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Paul-Benoit PobleChristophe Guignabert
Sep 5, 2006·American Journal of Physiology. Lung Cellular and Molecular Physiology·D CaseS Majka
Jul 17, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·Chun ZhouTroy Stevens
Jun 2, 2017·Internal Medicine·Masato NishiSeiji Hokimoto
Jun 6, 2017·Current Opinion in Pulmonary Medicine·Alice HuertasChristophe Guignabert
Sep 1, 2009·Current Protocols in Pharmacology·Markus ReyMartine Clozel
Aug 25, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Thenappan ThenappanE Kenneth Weir
Jun 24, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·Paul B DieffenbachLaura E Fredenburgh
Jan 15, 2003·Progress in Cardiovascular Diseases·T K Jeffery, N W Morrell

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