Short- and Long-term Hemodynamic Effects of Captopril in Patients with Pulmonary Hypertension and Selected Connective Tissue Disease

Alpert, Martin A.; Pressly, Thomas A.; Mukerji, Vaskar; Lambert, Charles R.; Mukerji, B

doi:10.1378/chest.102.5.1407

Cited by 72 publications

(32 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the 1980s, four small case-series (26 patients in total) reported on the haemodynamic effects of captopril in PAH. Three of the studies were positive and found a significant increase in cardiac output [60,61] and exercise capacity [62]. One study, however, did not observe any haemodynamic changes, neither positive nor negative [63].…”

Section: Renin-angiotensin-aldosterone Systemmentioning

confidence: 95%

Perspectives on novel therapeutic strategies for right heart failure in pulmonary arterial hypertension: lessons from the left heart

Handoko

Man

Allaart³

et al. 2010

European Respiratory Review

111

View full text Add to dashboard Cite

Right heart function is the main determinant of prognosis in pulmonary arterial hypertension (PAH). At present, no treatments are currently available that directly target the right ventricle, as we will demonstrate in this article.Meta-analysis of clinical trials in PAH revealed that current PAH medication seems to have limited cardiac-specific effects when analysed by the pump-function graph. Driven by the hypothesis that ''left'' and right heart failure might share important underlying pathophysiological mechanisms, we evaluated the clinical potential of left heart failure (LHF) therapies for PAH, based on currently available literature.As in LHF, the sympathetic nervous system and the renin-angiotension-aldosterone system are highly activated in PAH. From LHF we know that intervening in this process, e.g. by angiotensinconverting enzyme inhibition or b-blockade, is beneficial in the long run. Therefore, these medications could be also beneficial in PAH. Furthermore, the incidence of sudden cardiac death in PAH could be reduced by implantable cardioverter-defibrillators. Finally, pilot studies have demonstrated that interventricular dyssynchrony, present at end-stage PAH, responded favourably to cardiac resynchronisation therapy as well.In conclusion, therapies for LHF might be relevant for PAH. However, before they can be implemented in PAH management, safety and efficacy should be evaluated first in well-designed clinical trials.

show abstract

Section: Renin-angiotensin-aldosterone Systemmentioning

confidence: 95%

Perspectives on novel therapeutic strategies for right heart failure in pulmonary arterial hypertension: lessons from the left heart

Handoko

Man

Allaart³

et al. 2010

European Respiratory Review

111

View full text Add to dashboard Cite

show abstract

“…7 Two smaller case series have reported decreased pulmonary vascular resistance and improved RV function with captopril treatment in patients with RHF due to PAH. 36,37 Studies with patients with RHF due to an RV supporting the systemic circulation have reported no or only minor beneficial effect of treatment with ACE inhibitors or ARBs. 38,39 These contrasting results may reflect the issue of pulmonary versus cardiac effects of RAAS-blocking treatments.…”

Section: Effects Of Losartan Treatmentmentioning

confidence: 99%

Effects of Bisoprolol and Losartan Treatment in the Hypertrophic and Failing Right Heart

Andersen

Schultz

Andersen

et al. 2014

Journal of Cardiac Failure

View full text Add to dashboard Cite

“…The use of the angiotensin-converting enzyme (ACE) inhibitor captopril and the AT 1 R blocker losartan for treatment of patients with PH has produced mixed, albeit mostly positive, results (3,6,30,35,64). Pharmacological manipulation of the RAS in animal models of PH has also produced variable results but, on balance, suggests that the use of ACE inhibitors or angiotensin receptor blockers improves pulmonary hemodynamics and blunts the development of vascular remodeling (9,11,29,31,38,39,43,48,49,55,72).…”

mentioning

confidence: 99%

Oxidative stress contributes to pulmonary hypertension in the transgenic (mRen2)27 rat

DeMarco

Habibi

Whaley‐Connell

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Dellsperger KC. Oxidative stress contributes to pulmonary hypertension in the transgenic (mRen2)27 rat. Am J Physiol Heart Circ Physiol 294: H2659-H2668, 2008. First published April 18, 2008 doi:10.1152/ajpheart.00953.2007.-The transgenic (mRen2)27 (Ren2) rat overexpresses mouse renin in extrarenal tissues, causing increased local synthesis of ANG II, oxidative stress, and hypertension. However, little is known about the role of oxidative stress induced by the tissue renin-angiotensin system (RAS) as a contributing factor in pulmonary hypertension (PH). Using male Ren2 rats, we test the hypothesis that lung tissue RAS overexpression and resultant oxidative stress contribute to PH and pulmonary vascular remodeling. Mean arterial pressure (MAP), right ventricular systolic pressure (RVSP), and wall thickness of small pulmonary arteries (PA), as well as intrapulmonary NADPH oxidase activity and subunit protein expression and reactive oxygen species (ROS), were compared in age-matched Ren2 and Sprague-Dawley (SD) rats pretreated with the SOD/catalase mimetic tempol for 21 days. In placebo-treated Ren2 rats, MAP and RVSP, as well as intrapulmonary NADPH oxidase activity and subunits (Nox2, p22 phox , and Rac-1) and ROS, were elevated compared with placebo-treated SD rats (P Ͻ 0.05). Tempol decreased RVSP (P Ͻ 0.05), but not MAP, in Ren2 rats. Tempol also reduced intrapulmonary NADPH oxidase activity, Nox2, p22 phox , and Rac-1 protein expression, and ROS in Ren2 rats (P Ͻ 0.05). Compared with SD rats, the cross-sectional surface area of small PA was 38% greater (P Ͻ 0.001) and luminal surface area was 54% less (P Ͻ 0.001) in Ren2 rats. Wall surface area was reduced and luminal area was increased in tempol-treated SD and Ren2 rats compared with untreated controls (P Ͻ 0.05). Collectively, the results of this investigation support a seminal role for enhanced tissue RAS/oxidative stress as factors in development of PH and pulmonary vascular remodeling. renin; angiotensin II; NADPH oxidase CARDIOVASCULAR GENERATION of reactive oxygen species (ROS), such as superoxide and H 2 O 2 , has been implicated in the pathogenesis of hypertension, cardiac hypertrophy, pulmonary hypertension (PH), and heart failure (7). Molecular complexes known to generate superoxide within vascular endothelial and smooth muscle cells (SMC) include the NADPH oxidases (18), xanthine oxidase (32), the mitochondrial transport chain, and uncoupled nitric oxide synthase (NOS) (10,19). NADPH oxidase is a major source of ROS in the vasculature and is activated by hormones, growth factors, cytokines, and shear stress (16). An important stimulus for NADPH oxidase-generated ROS is ANG II. In fact, many of the deleterious effects of ANG II on vascular structure and function are mediated by ROS generation (16,73). ANG II causes rapid induction of NADPH oxidase-dependent superoxide synthesis via PKC (15) and more prolonged stimulation via transactivation of growth factors (62, 69). ANG II also causes redox-sensitive xanthine oxidase activation and endothelial N...

show abstract

Short- and Long-term Hemodynamic Effects of Captopril in Patients with Pulmonary Hypertension and Selected Connective Tissue Disease

Cited by 72 publications

References 26 publications

Perspectives on novel therapeutic strategies for right heart failure in pulmonary arterial hypertension: lessons from the left heart

Perspectives on novel therapeutic strategies for right heart failure in pulmonary arterial hypertension: lessons from the left heart

Effects of Bisoprolol and Losartan Treatment in the Hypertrophic and Failing Right Heart

Oxidative stress contributes to pulmonary hypertension in the transgenic (mRen2)27 rat

Contact Info

Product

Resources

About