© 1997 by European Society of Cardiology
Copyright © 1997, European Society of Cardiology
Haemodynamic and endocrine effects of type 1 angiotensin II receptor blockade in patients with hypoxaemic cor pulmonale
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, UK
Objectives: Angiotensin II (ANG II) is known to be a potent vasoconstrictor agent in the pulmonary circulation. Furthermore, type 1 ANG II receptor blockade with losartan attenuates acute hypoxic pulmonary vasoconstriction in normal subjects. The aim of this study was therefore to evaluate the haemodynamic and endocrine sequelae of type 1 ANG II receptor blockade in patients with hypoxaemic cor pulmonale. Methods: Nine patients with chronic obstructive pulmonary disease (COPD) age 67 ± 3 years with pulmonary hypertension and normal left ventricular systolic function were studied on two separate occasions in a double-blind, placebo-controlled, crossover study. They were randomised to receive either 50 mg of oral losartan or matched placebo. Pulsed wave Doppler echocardiography was used to measure cardiac output (CO), mean pulmonary artery pressure (MPAP) and hence systemic vascular resistance (SVR) and total pulmonary vascular resistance (TPR). Haemodynamic measurements and venous blood samples were taken at baseline and after 2 and 4 h. Results: Maximal effects were observed at 4 h where losartan compared to placebo resulted in a significant reduction in both MPAP (28.6 ± 2.0 vs 32.4 ± 1.5 mmHg) and TPR (428 ± 40 vs 510 ± 40 dyn·s·cm–5), respectively. Similarly losartan compared to placebo resulted in a significant reduction in MAP (87 ± 4.5 vs 93 ± 3.2 mmHg) and SVR (1293 ± 94 vs 1462 ± 112 dyn·s·cm–5), and significantly increased CO (5.58 ± 0.43 vs 5.31 ± 0.42 l/min). In addition, plasma aldosterone was significantly lower after treatment with losartan compared to placebo: 76 ± 23 vs 164 ± 43 pg/ml respectively. Conclusions: Thus, selective type 1 ANG II receptor blockade appears to have beneficial pulmonary and endocrine effects, suggesting a possible therapeutic role in the management of hypoxaemic cor pulmonale.
KEYWORDS Angiotensin II; Losartan; Angiotensin receptor; Pulmonary hypertension; Human
* Corresponding author. West Suffolk Hospital, Hardwick Lane, Bury St Edmunds, Suffolk, IP33 2QZ, UK. Tel. +44 1382 66011; Fax +44 1382 644972.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. E. Levitt, M. K. Gould, L. B. Ware, and M. A. Matthay Analytic Review: The Pathogenetic and Prognostic Value of Biologic Markers in Acute Lung Injury J Intensive Care Med, May 1, 2009; 24(3): 151 - 167. [Abstract] [PDF]
|
|
|
|
 |
|
 V. G. DeMarco, J. Habibi, A. T. Whaley-Connell, R. I. Schneider, R. L. Heller, J. P. Bosanquet, M. R. Hayden, K. Delcour, S. A. Cooper, B. T. Andresen, et al. Oxidative stress contributes to pulmonary hypertension in the transgenic (mRen2)27 rat Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2659 - H2668. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Imai, K. Kuba, and J. M. Penninger The discovery of angiotensin-converting enzyme 2 and its role in acute lung injury in mice Exp Physiol, May 1, 2008; 93(5): 543 - 548. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Adamzik, U. Frey, S. Sixt, L. Knemeyer, M. Beiderlinden, J. Peters, and W. Siffert ACE I/D but not AGT (-6)A/G polymorphism is a risk factor for mortality in ARDS Eur. Respir. J., March 1, 2007; 29(3): 482 - 488. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. J. Meyer and J. G. N. Garcia Wading into the Genomic Pool to Unravel Acute Lung Injury Genetics Proceedings of the ATS, January 1, 2007; 4(1): 69 - 76. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Andreas, C. Herrmann-Lingen, T. Raupach, L. Luthje, J. A. Fabricius, N. Hruska, W. Korber, B. Buchner, C-P. Criee, G. Hasenfuss, et al. Angiotensin II blockers in obstructive pulmonary disease: a randomised controlled trial Eur. Respir. J., May 1, 2006; 27(5): 972 - 979. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Andreas, S. D. Anker, P. D. Scanlon, and V. K. Somers Neurohumoral Activation as a Link to Systemic Manifestations of Chronic Lung Disease Chest, November 1, 2005; 128(5): 3618 - 3624. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. P. Marshall, P. Gohlke, R. C. Chambers, D. C. Howell, S. E. Bottoms, T. Unger, R. J. McAnulty, and G. J. Laurent Angiotensin II and the fibroproliferative response to acute lung injury Am J Physiol Lung Cell Mol Physiol, January 1, 2004; 286(1): L156 - L164. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. G. Fischer, H. V. Aken, and H. Burkle Management of Pulmonary Hypertension: Physiological and Pharmacological Considerations for Anesthesiologists Anesth. Analg., June 1, 2003; 96(6): 1603 - 1616. [Full Text] [PDF]
|
|
|
|
 |
|
 R. P. Marshall, S. Webb, G. J. Bellingan, H. E. Montgomery, B. Chaudhari, R. J. McAnulty, S. E. Humphries, M. R. Hill, and G. J. Laurent Angiotensin Converting Enzyme Insertion/Deletion Polymorphism Is Associated with Susceptibility and Outcome in Acute Respiratory Distress Syndrome Am. J. Respir. Crit. Care Med., September 1, 2002; 166(5): 646 - 650. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.A. Higham, D. Dawson, J. Joshi, P. Nihoyannopoulos, and N.W. Morrell Utility of echocardiography in assessment of pulmonary hypertension secondary to COPD Eur. Respir. J., March 1, 2001; 17(3): 350 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Mathew, N. Y.-T. Fan, N. Yuan, P. N. Chander, M. H. Gewitz, and C. T. Stier Jr. Inhibition of NOS enhances pulmonary vascular changes in stroke-prone spontaneously hypertensive rats Am J Physiol Lung Cell Mol Physiol, January 1, 2000; 278(1): L81 - L89. [Abstract] [Full Text] [PDF]
|
|