Lisinopril Attenuates Acute Hypoxic Pulmonary Vasoconstriction in Humans

Cargill, Robert I.; Lipworth, Brian J.

doi:10.1378/chest.109.2.424

Cited by 57 publications

(35 citation statements)

References 26 publications

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“…ACE-catalysed generation of angiotensinogen II can modulate the pulmonary vasoconstrictive response to hypoxia via the interaction with its receptor. 13 As Cargill and Lipworth showed that ACE inhibition might be a useful adjunctive treatment in hypoxaemic pulmonary hypertension, 14 it is reasonably expected that plasma ACE concentrations can serve as a strong predictor of HAPE risk. Observations have proposed that there is wide inter-individual variability of plasma ACE levels, and approximately half of this variability might be explained by the insertion/deletion (I/D) polymorphism of the human ACE gene.…”

Section: Introductionmentioning

confidence: 99%

Association of angiotensin-converting enzyme gene insertion/deletion polymorphism with high-altitude pulmonary oedema: a meta-analysis

Sun

Zhu

et al. 2011

J Renin Angiotensin Aldosterone Syst

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Background and objective: High-altitude pulmonary oedema (HAPE) is a non-cardiogenic hydrostatic oedema involving a genetic component. Considering the low incidence of HAPE, sample sizes in current reports are relatively limited. We aimed to assess the association between the angiotensin-converting enzyme (ACE) I/D polymorphism and HAPE via a meta-analysis of published and unpublished data. Materials and methods:We searched PubMed, CBM, CNKI, and Cochrane Library Database before 20 November 2010. A random-effects model was applied (STATA) and study quality was assessed in duplicate.Results: A total of five studies including 305 cases and 662 controls were meta-analysed. The summary odds ratio (OR) indicated that no significant differences in risk of developing HAPE were found between carriers of ACE D and I alleles (OR = 1.20; 95% confidence interval (CI), 0.98-1.48; p = 0.084). Lack of association persisted for genotypes under the recessive mode. However, genotype association under the dominant mode showed D allele carriers significantly conferred a 1.55-fold increased HAPE risk compared with II genotype carriers (95% CI, 1.15-2.08; p = 0.004). Funnel plot and Egger's test suggested no evidence of publication bias. Conclusions: Our results supported the notion that ACE D allele carriers were at significant increased risk of developing HAPE.

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Section: Introductionmentioning

confidence: 99%

Association of angiotensin-converting enzyme gene insertion/deletion polymorphism with high-altitude pulmonary oedema: a meta-analysis

Sun

Zhu

et al. 2011

J Renin Angiotensin Aldosterone Syst

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“…Cardiac output increases during acute hypoxic exposure in adult animal models and humans in order to maintain oxygen delivery at the peripheral tissues [14,15,28,29] . However, we have previously demonstrated that CO did not change significantly during acute hypoxia in healthy newborn piglets exposed to 14% O 2 [30] .…”

Section: Discussionmentioning

confidence: 99%

The Role of Angiotensin II Receptor-1 Blockade in the Hypoxic Pulmonary Vasoconstriction Response in Newborn Piglets

Camelo¹,

Hehre²,

Devia³

et al. 2007

Neonatology

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Background: Angiotensin-converting enzyme activity is increased in newborn infants with respiratory distress syndrome and in animals with alveolar hypoxia. Objective: To test whether angiotensin II (Ang II) mediates the pulmonary vasoconstriction induced by acute hypoxia in newborn piglets. Methods: Eight unanesthetized chronically instrumented newborn piglets (mean ± SEM; age 6.6 ± 0.6 days; weight 2,181 ± 174 g) were randomly assigned to receive a saline solution or the Ang II type 1 receptor (AT₁) antagonist, losartan, in a crossover study design, with an interval of at least 48 h between the first and second study. Pulmonary artery (Ppa), wedge, systemic arterial (Psa) and right atrial pressures, cardiac output (CO), pulmonary (PVR) and systemic (SVR) vascular resistances, and arterial blood gases were obtained in room air, before and during the saline or losartan infusion (6 mg/kg followed by 3 mg/kg/h), and during 6 h of hypoxia (FiO₂ = 0.11) and saline or losartan infusion. Data were analyzed by repeated measures analysis of variance. Results: The pulmonary vasoconstriction induced by acute hypoxia was significantly attenuated during losartan infusion, while Psa, SVR, CO, pH, PaCO₂, PaO₂ and base excess did not differ between groups. During room air, Ppa, PVR, Psa, SVR and CO values were not modified by saline or losartan infusion. Conclusion: These data suggest that the pulmonary vasoconstriction induced by acute hypoxia in newborn piglets is partially mediated by Ang II, acting via AT₁.

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“…A genotype-dependence in metabolic/ mechanical efficiency of skeletal muscle may partly contribute (Woods et al 2002b) Equally, a better maintained SaO 2 has been previously found amongst Iallele subjects during a rapid ascent to altitude (Woods et al 2002a), a phenomenon which may relate to genotype-dependent differences in hypoxic exertional ventilatory response (Rupert et al 1999;Patel et al 2003), and which may contribute to improved high-altitude performance (Montgomery et al 1998). Finally, higher ACE activity, as marked by the DD genotype, has been associated with exaggerated hypoxic pulmonary vasoconstriction (Cargill and Lipworth 1996), and possibly thus with increased ventilation-perfusion mismatch (Hlastala et al 2004).…”

Section: Discussionmentioning

confidence: 99%

Performance at altitude and angiotensin I-converting enzyme genotype

et al. 2004

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The "insertion" (I) rather than "deletion" (D) variant of the human angiotensin-converting enzyme (ACE) gene is associated with both lower tissue ACE activity and elite performance at high altitude. We examined whether the onset of acute mountain sickness (AMS), and further performance on reaching the summit of Mt. Blanc are influenced by the ACE I/D polymorphism. Two hundred and eighty-four climbers (235 males, [37.0 (11.0 years], (86 DD, 142 ID, 56 II)) had assessment of their AMS status upon arrival to the Gouter hut (3,807 m) on day 1, and again on day 2 after an attempted ascent to the summit of Mt. Blanc (4,807 m). Success in reaching the summit was genotype dependent (87.7% of DD, 94.9% of ID and 100% of II individuals; P=0.048); I allele frequency for those reaching the summit was 0.47 compared to 0.21 for those who did not (P=0.01). The onset of AMS on day 1 appeared to be dependent on genotype (P=0.003), but with those heterozygous being less affected. ACE genotype was not associated either with AMS onset or severity on day 2. Thus, ACE I/D genotype is associated with successful high altitude ascent in this prospective study-an association not explicable by genotype-dependence of AMS onset or severity. Values are given as mean (SD) unless otherwise stated.

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Lisinopril Attenuates Acute Hypoxic Pulmonary Vasoconstriction in Humans

Cited by 57 publications

References 26 publications

Association of angiotensin-converting enzyme gene insertion/deletion polymorphism with high-altitude pulmonary oedema: a meta-analysis

Association of angiotensin-converting enzyme gene insertion/deletion polymorphism with high-altitude pulmonary oedema: a meta-analysis

The Role of Angiotensin II Receptor-1 Blockade in the Hypoxic Pulmonary Vasoconstriction Response in Newborn Piglets

Performance at altitude and angiotensin I-converting enzyme genotype

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