scholarly journals Cellular Pathways Promoting Pulmonary Vascular Remodeling by Hypoxia

Physiology ◽  
2020 ◽  
Vol 35 (4) ◽  
pp. 222-233
Author(s):  
Larissa A. Shimoda
Keyword(s):  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Vascular Remodeling ◽  
Pulmonary Arterial Pressure ◽  
Right Heart Failure ◽  
Right Heart ◽  
Pulmonary Vascular Remodeling ◽  
Vascular Stiffening ◽  
Pulmonary Arterial ◽  
Cellular Pathways

Exposure to hypoxia increases pulmonary vascular resistance, leading to elevated pulmonary arterial pressure and, potentially, right heart failure. Vascular remodeling is an important contributor to the increased pulmonary vascular resistance. Hyperproliferation of smooth muscle, endothelial cells, and fibroblasts, and deposition of extracellular matrix lead to increased wall thickness, extension of muscle into normally non-muscular arterioles, and vascular stiffening. This review highlights intrinsic and extrinsic modulators contributing to the remodeling process.

scholarly journals Purinergic Dysfunction in Pulmonary Arterial Hypertension

2020 ◽  
Vol 9 (18) ◽  
Author(s):  
Zongye Cai ◽  
Ly Tu ◽  
Christophe Guignabert ◽  
Daphne Merkus ◽  
Zhichao Zhou
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Right Ventricle ◽  
Arterial Hypertension ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Vascular Remodeling ◽  
Purinergic Signaling ◽  
Receptor Activation ◽  
Pulmonary Vascular Remodeling ◽  
Pulmonary Arterial

Abstract Pulmonary arterial hypertension (PAH) is a life‐threatening disease characterized by increased pulmonary arterial pressure and pulmonary vascular resistance, which result in an increase in afterload imposed onto the right ventricle, leading to right heart failure. Current therapies are incapable of reversing the disease progression. Thus, the identification of novel and potential therapeutic targets is urgently needed. An alteration of nucleotide‐ and nucleoside‐activated purinergic signaling has been proposed as a potential contributor in the pathogenesis of PAH. Adenosine‐mediated purinergic 1 receptor activation, particularly A 2A R activation, reduces pulmonary vascular resistance and attenuates pulmonary vascular remodeling and right ventricle hypertrophy, thereby exerting a protective effect. Conversely, A 2B R activation induces pulmonary vascular remodeling, and is therefore deleterious. ATP‐mediated P2X 7 R activation and ADP‐mediated activation of P2Y 1 R and P2Y 12 R play a role in pulmonary vascular tone, vascular remodeling, and inflammation in PAH. Recent studies have revealed a role of ectonucleotidase nucleoside triphosphate diphosphohydrolase, that degrades ATP/ADP, in regulation of pulmonary vascular remodeling. Interestingly, existing evidence that adenosine activates erythrocyte A 2B R signaling, counteracting hypoxia‐induced pulmonary injury, and that ATP release is impaired in erythrocyte in PAH implies erythrocyte dysfunction as an important trigger to affect purinergic signaling for pathogenesis of PAH. The present review focuses on current knowledge on alteration of nucleot(s)ide‐mediated purinergic signaling as a potential disease mechanism underlying the development of PAH.

scholarly journals Clinical application of pulmonary vascular resistance in patients with pulmonary arterial hypertension

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jianying Deng
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Pulmonary Vascular Resistance ◽  
Clinical Application ◽  
Vascular Resistance ◽  
Right Heart Failure ◽  
Pulmonary Vascular Disease ◽  
Right Heart ◽  
Pulmonary Arteriole ◽  
Pulmonary Arterial

AbstractPulmonary arterial hypertension is a type of malignant pulmonary vascular disease, which is mainly caused by the increase of pulmonary vascular resistance due to the pathological changes of the pulmonary arteriole itself, which eventually leads to right heart failure and death. As one of the diagnostic indicators of hemodynamics, pulmonary vascular resistance plays an irreplaceable role in the pathophysiology, diagnosis and treatment of pulmonary arterial hypertension. It provides more references for the evaluation of pulmonary arterial hypertension patients. This article summarizes the clinical application of pulmonary vascular resistance in patients with pulmonary arterial hypertension.

Effects of Hemoglobin on Pulmonary Arterial Pressure and Pulmonary Vascular Resistance in Patients with Chronic Emphysema

Respiration ◽  
2000 ◽  
Vol 67 (5) ◽  
pp. 502-506 ◽  
Author(s):  
Akira Nakamura ◽  
Norio Kasamatsu ◽  
Ikko Hashizume ◽  
Takushi Shirai ◽  
Suguru Hanzawa ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Arterial Pressure ◽  
Pulmonary Arterial

Low exercise pulmonary resistance is not dependent on vasodilator prostaglandins

1983 ◽  
Vol 55 (2) ◽  
pp. 558-561 ◽  
Author(s):  
J. Lindenfeld ◽  
J. T. Reeves ◽  
L. D. Horwitz
Keyword(s):  
Cardiac Output ◽  
Arterial Pressure ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Arterial Pressure ◽  
Cyclooxygenase Inhibitors ◽  
Pulmonary Resistance ◽  
Before And After ◽  
Pulmonary Arterial

In resting conscious dogs, administration of cyclooxygenase inhibitors results in modest increases in pulmonary arterial pressure and pulmonary vascular resistance, suggesting that vasodilator prostaglandins play a role in maintaining the low vascular resistance in the pulmonary bed. To assess the role of these vasodilator prostaglandins on pulmonary vascular resistance during exercise, we studied seven mongrel dogs at rest and during exercise before and after intravenous meclofenamate (5 mg/kg). Following meclofenamate, pulmonary vascular resistance rose both at rest (250 24 vs. 300 +/- 27 dyn . s . cm-5, P less than 0.01) and with exercise (190 +/- 9 vs. 210 +/- 12 dyn . s . cm-5, P less than 0.05). Systemic vascular resistance rose slightly following meclofenamate both at rest and during exercise. There were no changes in cardiac output. The effects of cyclooxygenase inhibition, although significant, were less during exercise than at rest. This suggests that the normal fall in pulmonary vascular resistance during exercise depends largely on factors other than vasodilator prostaglandins.

scholarly journals Mechanisms of right heart disease in pulmonary hypertension (2017 Grover Conference Series)

2017 ◽  
Vol 8 (1) ◽  
pp. 204589321775312 ◽  
Author(s):  
Kewal Asosingh ◽  
Serpil Erzurum
Keyword(s):  
Heart Disease ◽  
Right Ventricle ◽  
Vascular Remodeling ◽  
Cardiac Tissue ◽  
Direct Consequence ◽  
Right Heart Failure ◽  
Right Heart ◽  
Pulmonary Vascular Remodeling ◽  
Right Ventricle Dysfunction ◽  
The Right

Current dogma is that pathological hypertrophy of the right ventricle is a direct consequence of pulmonary vascular remodeling. However, progression of right ventricle dysfunction is not always lung-dependent. Increased afterload caused by pulmonary vascular remodeling initiates the right ventricle hypertrophy, but determinants leading to adaptive or maladaptive hypertrophy and failure remain unknown. Ischemia in a hypertrophic right ventricle may directly contribute to right heart failure. Rapidly enlarging cardiomyocytes switch from aerobic to anaerobic energy generation resulting in cell growth under relatively hypoxic conditions. Cardiac muscle reacts to an increased afterload by over-activation of the sympathetic system and uncoupling and downregulation of β-adrenergic receptors. Recent studies suggest that β blocker therapy in PH is safe, well tolerated, and preserves right ventricle function and cardiac output by reducing right ventricular glycolysis. Fibrosis, an evolutionary conserved process in host defense and wound healing, is dysregulated in maladaptive cardiac tissue contributing directly to right ventricle failure. Despite several mechanisms having been suggested in right heart disease, the causes of maladaptive cardiac remodeling remain unknown and require further research.

Pulmonary vascular reactivity and hemodynamic changes in elastase-induced emphysema in hamsters

1992 ◽  
Vol 73 (4) ◽  
pp. 1474-1480 ◽  
Author(s):  
C. M. Tseng ◽  
S. Qian ◽  
W. Mitzner
Keyword(s):  
Angiotensin Ii ◽  
Arterial Pressure ◽  
Right Ventricular ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Ventricular Hypertrophy ◽  
Vascular Reactivity ◽  
Pulmonary Arterial Pressure ◽  
Pressor Responses ◽  
Pulmonary Arterial

Changes in pulmonary hemodynamics and vascular reactivity in emphysematous hamsters were studied in an isolated lung preparation perfused at constant flow with blood and 3% dextran. Hamsters were treated with intratracheal porcine pancreatic elastase at 70 days of age, and experimental studies were conducted at 1, 3, and 8 mo after treatment. Baseline pulmonary arterial pressure in elastase-treated lungs was increased compared with saline-treated control lungs 1 mo after treatment, but this increase did not progress at 3 and 8 mo. Increases in pulmonary arterial pressure in elastase-treated lungs were temporally correlated with the morphological development of emphysema and right ventricular hypertrophy; both of these were evident at 1 mo after treatment and showed little change thereafter. Pressor responses to hypoxia and angiotensin II were not different between elastase-treated and control lungs at 1 and 3 mo. At 8 mo, however, pressor responses in emphysematous lungs to 0% O2 (but not to angiotensin II) were significantly increased. This was the result of a lack of the normal age-related fall in the hypoxic pressor response. Our results suggest that the right ventricular hypertrophy found in these emphysematous animals results from a chronically increased pulmonary vascular resistance. Furthermore, increases in pulmonary vascular resistance in the early development of emphysema are likely a result of the loss of vascular beds and supporting connective tissue.

Evidence that hypoxic pulmonary vascular remodeling in rats is polyamine dependent

1987 ◽  
Vol 62 (4) ◽  
pp. 1562-1568 ◽  
Author(s):  
J. E. Atkinson ◽  
J. W. Olson ◽  
R. J. Altiere ◽  
M. N. Gillespie
Keyword(s):  
Arterial Pressure ◽  
Right Ventricular ◽  
Vascular Remodeling ◽  
Ventricular Hypertrophy ◽  
Chronic Hypoxia ◽  
Pulmonary Arterial Pressure ◽  
Right Ventricular Hypertrophy ◽  
Polyamine Biosynthesis ◽  
Pulmonary Vascular Remodeling ◽  
Pulmonary Arterial

This study tested the hypothesis that the polyamines, a family of low-molecular-weight organic cations with documented regulatory roles in cell growth and differentiation, are mediators of chronic hypoxia-induced pulmonary vascular remodeling. Relative to room air controls, chronically hypoxic animals (inspired O2 fraction = 0.1; 21 days) exhibited higher pulmonary arterial pressures (measured in room air), thicker medial layers in pulmonary arteries of 50–100 microns diam, increased hematocrits, and right ventricular hypertrophy. In addition, lung contents of the polyamines, putrescine, spermidine, and spermine were greater in hypoxic animals than in controls. alpha-Difluoromethylornithine (DFMO), an inhibitor of polyamine synthesis, attenuated the hypoxia-induced elevations in lung putrescine and spermidine content and blunted the increases in pulmonary arterial pressure and medial thickness. Neither the increased hematocrit nor right ventricular hypertrophy associated with chronic hypoxia were abrogated by DFMO. In addition, DFMO failed to influence vasoconstrictor responses provoked by acute hypoxic ventilation in isolated, buffer-perfused rat lungs. These observations suggest that depression of polyamine biosynthesis with DFMO blunts the sustained increase in pulmonary arterial pressure by attenuating hypoxia-induced medial thickening.

scholarly journals Hypoxia-induced mitogenic factor (FIZZ1/RELMα) induces endothelial cell apoptosis and subsequent interleukin-4-dependent pulmonary hypertension

2014 ◽  
Vol 306 (12) ◽  
pp. L1090-L1103 ◽  
Author(s):  
Kazuyo Yamaji-Kegan ◽  
Eiki Takimoto ◽  
Ailan Zhang ◽  
Noah C. Weiner ◽  
Lucas W. Meuchel ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Endothelial Cell ◽  
Vascular Remodeling ◽  
Lung Inflammation ◽  
Critical Role ◽  
Right Heart Failure ◽  
Right Heart ◽  
Pulmonary Vascular Remodeling ◽  
Mitogenic Factor

Pulmonary hypertension (PH) is characterized by elevated pulmonary artery pressure that leads to progressive right heart failure and ultimately death. Injury to endothelium and consequent wound repair cascades have been suggested to trigger pulmonary vascular remodeling, such as that observed during PH. The relationship between injury to endothelium and disease pathogenesis in this disorder remains poorly understood. We and others have shown that, in mice, hypoxia-induced mitogenic factor (HIMF, also known as FIZZ1 or RELMα) plays a critical role in the pathogenesis of lung inflammation and the development of PH. In this study, we dissected the mechanism by which HIMF and its human homolog resistin (hRETN) induce pulmonary endothelial cell (EC) apoptosis and subsequent lung inflammation-mediated PH, which exhibits many of the hallmarks of the human disease. Systemic administration of HIMF caused increases in EC apoptosis and interleukin (IL)-4-dependent vascular inflammatory marker expression in mouse lung during the early inflammation phase. In vitro, HIMF, hRETN, and IL-4 activated pulmonary microvascular ECs (PMVECs) by increasing angiopoietin-2 expression and induced PMVEC apoptosis. In addition, the conditioned medium from hRETN-treated ECs had elevated levels of endothelin-1 and caused significant increases in pulmonary vascular smooth muscle cell proliferation. Last, HIMF treatment caused development of PH that was characterized by pulmonary vascular remodeling and right heart failure in wild-type mice but not in IL-4 knockout mice. These data suggest that HIMF contributes to activation of vascular inflammation at least in part by inducing EC apoptosis in the lung. These events lead to subsequent PH.

Pregnancy blunts pulmonary vascular reactivity in dogs

1980 ◽  
Vol 239 (3) ◽  
pp. H297-H301 ◽  
Author(s):  
L. G. Moore ◽  
J. T. Reeves
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Circulation ◽  
Vascular Reactivity ◽  
Pulmonary Arterial Pressure ◽  
Acute Hypoxia ◽  
Limited Data ◽  
Mean Pulmonary Arterial Pressure ◽  
Pulmonary Arterial

Pregnancy decreases systemic vascular reactivity but comparatively little is known about the effects of pregnancy on the pulmonary circulation. Pulmonary vascular resistance (PVR) during acute hypoxia was lower (P < 0.01) in eight intact anesthetized pregnant dogs compared to the same animals postpartum. Mean pulmonary arterial pressure (Ppa) and PVR during infusion of prostaglandin (PG) F2 alpha were also reduced during pregnancy. Nonpregnant female dogs (n = 5) treated with estrogen (0.001 mg x kg-1 x da-1) for 2 wk had decreased Ppa (P < 0.01) during acute hypoxia compared to control measurements, but PVR was unchanged during hypoxia and PGF2 alpha infusion. Treatment with progesterone in four dogs had no effect on pulmonary vascular reactivity to hypoxia or PGF2 alpha. Inhibition of circulating PG with meclofenamate in four dogs during pregnancy did not appear to restore pulmonary vascular reactivity. Blunted pulmonary vascular reactivity is suggested by the limited data available for women, but is not seen in pregnant cows. We conclude that pregnancy decreases pulmonary as well as systemic vascular reactivity in the dog, but the mechanism is unclear.

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