Related Experiment Video
Updated: Mar 28, 2026
Increasing Pulmonary Artery Pulsatile Flow Improves Hypoxic Pulmonary Hypertension in Piglets
Published on: May 11, 2015
Vascular Dysfunction in Pneumocystis-Associated Pulmonary Hypertension Is Related to Endothelin Response and
Dan W Siemsen1, Erin Dobrinen1, Soo Han1
1Department of Microbiology and Immunology, Montana State University, Bozeman, Montana.
Abstract:
Pulmonary hypertension subsequent to an infectious disease can be due to vascular structural remodeling or to functional alterations within various vascular cell types. In our previous mouse model of Pneumocystis-associated pulmonary hypertension, we found that vascular remodeling was not responsible for observed increases in right ventricular pressures. Here, we report that the vascular dysfunction we observed could be explained by an enhanced response to endothelin-1 (20% greater reduction in lumen diameter, P ≤ 0.05), corresponding to an up-regulation of similar magnitude (P ≤ 0.05) of the endothelin A receptor in the lung tissue. This effect was potentially augmented by a decrease in production of the pulmonary vasodilator adrenomedullin of almost 70% (P ≤ 0.05). These changes did not occur in interferon-γ knockout mice similarly treated, which do not develop pulmonary hypertension under these circumstances. Surprisingly, we did not observe any relevant changes in the vascular endothelial nitric oxide synthase vasodilatory response, which is a common potential site of inflammatory alterations to pulmonary vascular function. Our results indicate the diverse mechanisms by which inflammatory responses to prior infections can cause functionally relevant changes in vascular responses in the lung, promoting the development of pulmonary hypertension.
Insights
Infection-induced pulmonary hypertension involves altered lung vascular function, not remodeling. Enhanced endothelin-1 signaling and reduced adrenomedullin contribute to this dysfunction, highlighting key mechanisms in post-infectious pulmonary hypertension.
Area of Science:
- Pulmonary vascular disease
- Infectious disease immunology
- Cardiovascular research
Background:
- Pulmonary hypertension (PH) can follow infections, involving vascular structural changes or functional alterations.
- Previous studies indicated vascular remodeling is not the cause of PH in a Pneumocystis infection mouse model.
Purpose of the Study:
- To investigate the functional vascular mechanisms underlying infectious disease-associated pulmonary hypertension.
- To elucidate the roles of endothelin-1, adrenomedullin, and nitric oxide pathways in this condition.
Main Methods:
- Utilized a mouse model of Pneumocystis-associated pulmonary hypertension.
- Assessed vascular responses to endothelin-1 and measured endothelin A receptor and adrenomedullin levels.
- Examined vascular endothelial nitric oxide synthase activity.
- Compared wild-type and interferon-γ knockout mice.
Main Results:
- Vascular dysfunction, not remodeling, explained increased right ventricular pressures.
- Enhanced endothelin-1 response (20% greater lumen reduction) and upregulated endothelin A receptor (similar magnitude) were observed.
- Pulmonary vasodilator adrenomedullin production decreased by nearly 70%.
- Interferon-γ knockout mice did not develop PH, and vascular endothelial nitric oxide synthase function remained unchanged.
Conclusions:
- Inflammatory responses to infections can cause functionally relevant pulmonary vascular changes, promoting PH.
- Enhanced endothelin-1 signaling and reduced adrenomedullin are key contributors to post-infectious PH.
- Nitric oxide pathways are not significantly involved in this specific model of infectious PH.
More Related Videos
07:41A Model of Reverse Vascular Remodeling in Pulmonary Hypertension Due to Left Heart Disease by Aortic Debanding in Rats
Published on: March 1, 2022
07:09Assessment of Pulmonary Capillary Blood Volume, Membrane Diffusing Capacity, and Intrapulmonary Arteriovenous Anastomoses During Exercise
Published on: February 20, 2017
Related Concept Videos
01:18Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
01:29Heart Failure II: Pathophysiology
01:30Pulmonary Hypertension: Classification and Pathogenesis
There are various classifications for PH, each relating to different underlying causes and also...
01:22Mitral Stenosis I: Introduction
01:28Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...
01:19Factors Affecting Pulmonary Ventilation
Alveolar Surface Tension
The alveolar fluid lines the luminal surface of the alveoli and exerts a force called surface tension. This force is caused by the polar water molecules in the liquid being more strongly attracted to each...