Document Detail

Haemodynamic and endocrine effects of type 1 angiotensin II receptor blockade in patients with hypoxaemic cor pulmonale.
MedLine Citation:
PMID:  9059545     Owner:  NLM     Status:  MEDLINE    
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 +/-, 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, 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.
D G Kiely; R I Cargill; N M Wheeldon; W J Coutie; B J Lipworth
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial    
Journal Detail:
Title:  Cardiovascular research     Volume:  33     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  1997 Jan 
Date Detail:
Created Date:  1997-03-28     Completed Date:  1997-03-28     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  201-8     Citation Subset:  IM    
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, University of Dundee, Scotland, UK.
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MeSH Terms
Aldosterone / blood
Angiotensin II / antagonists & inhibitors*
Antihypertensive Agents / therapeutic use*
Biphenyl Compounds / therapeutic use*
Cross-Over Studies
Double-Blind Method
Echocardiography, Doppler, Pulsed
Hypertension, Pulmonary / blood,  drug therapy,  ultrasonography
Imidazoles / therapeutic use*
Lung Diseases, Obstructive / blood,  drug therapy,  ultrasonography
Pulmonary Heart Disease / blood,  drug therapy*,  ultrasonography
Receptors, Angiotensin / antagonists & inhibitors*
Tetrazoles / therapeutic use*
Vascular Resistance / drug effects
Reg. No./Substance:
0/Antihypertensive Agents; 0/Biphenyl Compounds; 0/Imidazoles; 0/Receptors, Angiotensin; 0/Tetrazoles; 11128-99-7/Angiotensin II; 114798-26-4/Losartan; 52-39-1/Aldosterone

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