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Losartan exerts no protective effects against acute pulmonary embolism-induced hemodynamic changes

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Abstract

The acute obstruction of pulmonary vessels by venous thrombi is a critical condition named acute pulmonary embolism (APE). During massive APE, severe pulmonary hypertension may lead to death secondary to right heart failure and circulatory shock. APE-induced pulmonary hypertension is aggravated by active pulmonary vasoconstriction. While blocking the effects of some vasoconstrictors exerts beneficial effects, no previous study has examined whether angiotensin II receptor blockers protect against the hemodynamic changes associated with APE. We examined the effects exerted by losartan on APE-induced hemodynamic changes. Hemodynamic evaluations were performed in non-embolized lambs treated with saline (n = 4) and in lambs that were embolized with silicon microspheres and treated with losartan (30 mg/kg followed by 1 mg/kg/h, n = 5) or saline (n = 7) infusions. The plasma and lung angiotensin-converting enzyme (ACE) activity were assessed using a fluorometric method. APE increased mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance index (PVRI) by 21 ± 2 mmHg and 375 ± 20 dyn s cm−5 m−2, respectively (P < 0.05). Losartan decreased MPAP significantly (by approximately 15%), without significant changes in PVRI and tended to decrease cardiac index (P > 0.05). Lung and plasma ACE activity were similar in both embolized and non-embolized animals. Our findings show evidence of lack of activation of the renin–angiotensin system during APE. The lack of significant effects of losartan on the pulmonary vascular resistance suggests that losartan does not protect against the hemodynamic changes found during APE.

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Acknowledgments

This study was supported by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Conselho Nacional de Dsenvolvimento Cientifico e Tecnologico (CNPq), and Coordenadoria de Aperfeiçoamento de Pessoal de Nivel Superior (CAPES).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmacology, Campus Centro-Oeste Dona Lindu, Federal University of Sao Joao Del Rei, Rua Sebastiao Goncalves Coelho, 400, 35501-296, Divinopolis, MG, Brazil

    Carlos A. Dias-Junior

  2. Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirao Preto, SP, Brazil

    Evandro M. Neto-Neves, Marcelo F. Montenegro & Jose E. Tanus-Santos

Authors
  1. Carlos A. Dias-Junior
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  2. Evandro M. Neto-Neves
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  3. Marcelo F. Montenegro
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  4. Jose E. Tanus-Santos
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Correspondence to Jose E. Tanus-Santos.

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Dias-Junior, C.A., Neto-Neves, E.M., Montenegro, M.F. et al. Losartan exerts no protective effects against acute pulmonary embolism-induced hemodynamic changes. Naunyn-Schmiedeberg's Arch Pharmacol 385, 211–217 (2012). https://doi.org/10.1007/s00210-011-0695-x

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  • DOI: https://doi.org/10.1007/s00210-011-0695-x

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