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Angiotensin II and monocrotaline-induced pulmonary hypertension: effect of losartan (DuP 753), a nonpeptide angiotensin type 1 receptor antagonist.
J Pharmacol Exp Ther. 1992 Sep; 262(3):1168-72.JP

Abstract

Administration of the pyrrolizidine alkaloid monocrotaline (MCT) to rats results in hypertensive pulmonary vascular disease characterized by a structurally based increase in pulmonary vascular resistance and right ventricular hypertrophy. Alterations in lung angiotensin converting enzyme activity in MCT-treated rats have suggested a role for angiotensin II (AII) in the pathogenesis of this model of hypertensive pulmonary vascular disease. To determine if increases in AII contribute to the development of pulmonary hypertension in MCT-treated rats, we examined the effect of chronic administration of the nonpeptide AII receptor antagonist Losartan on indices of pulmonary hypertension, Losartan (DuP 753; 10 mg/kg s.c.) administration for 21 days did not prevent the development of hypertensive pulmonary vascular disease in MCT-treated rats. However, 18 hr after the last dose of Losartan, AII (0.1 micrograms/kg i.v.)-induced pressor responses were inhibited by 63% in Losartan-treated rats. Losartan administration in MCT-treated rats did not prevent increases in pulmonary artery pressure or development of right ventricular hypertrophy. Additionally, increases in medial arterial thickness in pulmonary artery vessels (less than 50 microns and 50-100 microns external diameter) from MCT-treated rats were still evident in Losartan-treated rats. However, Losartan administration decreased medial pulmonary artery thickness of 50 to 100 microns external diameter vessels in control rats. These results demonstrate that AII. acting at the AT1 receptor subtype, does not contribute to pulmonary hypertension in this animal model.

Authors+Show Affiliations

Division of Pharmacology and Experimental Therapeutics, College of Pharmacy, University of Kentucky, Lexington.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

1527721

Citation

Cassis, L A., et al. "Angiotensin II and Monocrotaline-induced Pulmonary Hypertension: Effect of Losartan (DuP 753), a Nonpeptide Angiotensin Type 1 Receptor Antagonist." The Journal of Pharmacology and Experimental Therapeutics, vol. 262, no. 3, 1992, pp. 1168-72.
Cassis LA, Rippetoe PE, Soltis EE, et al. Angiotensin II and monocrotaline-induced pulmonary hypertension: effect of losartan (DuP 753), a nonpeptide angiotensin type 1 receptor antagonist. J Pharmacol Exp Ther. 1992;262(3):1168-72.
Cassis, L. A., Rippetoe, P. E., Soltis, E. E., Painter, D. J., Fitz, R., & Gillespie, M. N. (1992). Angiotensin II and monocrotaline-induced pulmonary hypertension: effect of losartan (DuP 753), a nonpeptide angiotensin type 1 receptor antagonist. The Journal of Pharmacology and Experimental Therapeutics, 262(3), 1168-72.
Cassis LA, et al. Angiotensin II and Monocrotaline-induced Pulmonary Hypertension: Effect of Losartan (DuP 753), a Nonpeptide Angiotensin Type 1 Receptor Antagonist. J Pharmacol Exp Ther. 1992;262(3):1168-72. PubMed PMID: 1527721.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Angiotensin II and monocrotaline-induced pulmonary hypertension: effect of losartan (DuP 753), a nonpeptide angiotensin type 1 receptor antagonist. AU - Cassis,L A, AU - Rippetoe,P E, AU - Soltis,E E, AU - Painter,D J, AU - Fitz,R, AU - Gillespie,M N, PY - 1992/9/1/pubmed PY - 1992/9/1/medline PY - 1992/9/1/entrez SP - 1168 EP - 72 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 262 IS - 3 N2 - Administration of the pyrrolizidine alkaloid monocrotaline (MCT) to rats results in hypertensive pulmonary vascular disease characterized by a structurally based increase in pulmonary vascular resistance and right ventricular hypertrophy. Alterations in lung angiotensin converting enzyme activity in MCT-treated rats have suggested a role for angiotensin II (AII) in the pathogenesis of this model of hypertensive pulmonary vascular disease. To determine if increases in AII contribute to the development of pulmonary hypertension in MCT-treated rats, we examined the effect of chronic administration of the nonpeptide AII receptor antagonist Losartan on indices of pulmonary hypertension, Losartan (DuP 753; 10 mg/kg s.c.) administration for 21 days did not prevent the development of hypertensive pulmonary vascular disease in MCT-treated rats. However, 18 hr after the last dose of Losartan, AII (0.1 micrograms/kg i.v.)-induced pressor responses were inhibited by 63% in Losartan-treated rats. Losartan administration in MCT-treated rats did not prevent increases in pulmonary artery pressure or development of right ventricular hypertrophy. Additionally, increases in medial arterial thickness in pulmonary artery vessels (less than 50 microns and 50-100 microns external diameter) from MCT-treated rats were still evident in Losartan-treated rats. However, Losartan administration decreased medial pulmonary artery thickness of 50 to 100 microns external diameter vessels in control rats. These results demonstrate that AII. acting at the AT1 receptor subtype, does not contribute to pulmonary hypertension in this animal model. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/1527721/Angiotensin_II_and_monocrotaline_induced_pulmonary_hypertension:_effect_of_losartan__DuP_753__a_nonpeptide_angiotensin_type_1_receptor_antagonist_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=1527721 DB - PRIME DP - Unbound Medicine ER -