scholarly journals Hypercapnia attenuates hypoxic pulmonary hypertension by inhibiting lung radical injury

2009 ◽  
pp. S79-S86 ◽  
Author(s):  
M Chovanec ◽  
J Novotná ◽  
J Wilhelm ◽  
V Hampl ◽  
M Vízek ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arteries ◽  
Male Rats ◽  
Pulmonary Vasculature ◽  
Hypoxic Pulmonary Hypertension ◽  
Hypoxic Injury ◽  
Arterial Blood ◽  
Hypoxic Environment ◽  
Pulmonary Arterial ◽  
The Right

Chronic lung hypoxia results in hypoxic pulmonary hypertension. Concomitant chronic hypercapnia partly inhibits the effect of hypoxia on pulmonary vasculature. Adult male rats exposed to 3 weeks hypoxia (Fi02=0.1) combined with hypercapnia (FiC02=0.04-0.05) had lower pulmonary arterial blood pressure, increased weight of the right heart ventricle, and less pronounced structural remodeling of the peripheral pulmonary arteries compared with rats exposed only to chronic hypoxia (Fi02=0.1). According to our hypothesis, hypoxic pulmonary hypertension is triggered by hypoxic injury to the walls of the peripheral pulmonary arteries. Hypercapnia inhibits release of both oxygen radicals and nitric oxide at the beginning of exposure to the hypoxic environment. The plasma concentration of nitrotyrosine, the marker of peroxynitrite activity, is lower in hypoxic rats exposed to hypercapnia than in those exposed to hypoxia alone. Hypercapnia blunts hypoxia-induced collagenolysis in the walls of prealveolar pulmonary arteries. We conclude that hypercapnia inhibits the development of hypoxic pulmonary hypertension by the inhibition of radical injury to the walls of peripheral pulmonary arteries.

CGRP and somatostatin modulate chronic hypoxic pulmonary hypertension

1992 ◽  
Vol 263 (3) ◽  
pp. H681-H690 ◽  
Author(s):  
S. Tjen-A-Looi ◽  
R. Ekman ◽  
H. Lippton ◽  
J. Cary ◽  
I. Keith
Keyword(s):  
Pulmonary Hypertension ◽  
Main Pulmonary Artery ◽  
Pulmonary Vasculature ◽  
Hypoxic Pulmonary Hypertension ◽  
Calcitonin Gene ◽  
Pulmonary Arterial ◽  
Pentobarbital Sodium Anesthesia ◽  
The Right ◽  
Potential Interactions

Chronic hypoxic pulmonary hypertension (PH), associated with increased pulmonary arterial pressure (PPA) and right ventricular hypertrophy (RVH), correlates significantly with calcitonin gene-related peptide (CGRP) and somatostatin (SOM) levels in lung and blood. CGRP's role in regulation of PPA in chronic hypoxia and its potential interactions with SOM were investigated. CGRP, its antibody (ab) and blocker, CGRP-(8–37), SOM-14, SOM-28, and SOM-ab, respectively, were infused into the pulmonary circulation of hypobaric hypoxia rats for 4, 8, and 16 days. Thereafter, under pentobarbital sodium anesthesia, PPA was measured in the right ventricle and main pulmonary artery. Chronic CGRP infusion prevented PH at all times, whereas immunoneutralization and receptor blocking exacerbated PH. SOM-28 also exacerbated while SOM-14 and SOM-ab decreased PH. RVH generally reflected the PPA. Radioimmunoassay confirmed successful infusion of the peptides with negligible peptide degradation in the pumps throughout 16 days and showed complete immunoneutralization of CGRP with its ab. Peptide levels in lung tissue suggest inhibition of CGRP release by SOM-28 and increased plasma SOM with CGRP infusion. In vitro pharmacological studies suggest that CGRP exerts a receptor-mediated nonadrenergic, nonmuscarinic vasodilatory effect in the lung which is independent of endothelium-derived relaxing factor and does not involve ATP-dependent potassium channels. We conclude that endogenous CGRP plays an important role in pulmonary pressure homeostasis during hypoxia, by directly dilating pulmonary vasculature, thus ameliorating the development of chronic hypoxic pulmonary hypertension in rats.

Expressions of adrenomedullin mRNA and protein in rats with hypobaric hypoxia-induced pulmonary hypertension

2004 ◽  
Vol 286 (6) ◽  
pp. H2159-H2168 ◽  
Author(s):  
Kuniaki Nakanishi ◽  
Hiroshi Osada ◽  
Maki Uenoyama ◽  
Fumiko Kanazawa ◽  
Nobuhiro Ohrui ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Late Phase ◽  
Pulmonary Arteries ◽  
Hypoxic Environment ◽  
Male Wistar Rats ◽  
Pulmonary Arterial ◽  
The Right ◽  
The Brain ◽  
Altitude Level

Experimental pulmonary hypertension induced in a hypobaric hypoxic environment (HHE) is characterized by structural remodeling of the heart and pulmonary arteries. Adrenomedullin (AM) has diuretic, natriuretic, and hypotensive effects. To study the possible effects of HHE on the AM synthesis system, 150 male Wistar rats were housed in a chamber at the equivalent of a 5,500-m altitude level for 21 days. After 14 days of exposure to HHE, pulmonary arterial pressure (PAP) was significantly increased (compared with control rats). The plasma AM protein level was significantly increased on day 21 of exposure to HHE. In the right ventricle (RV), right atrium, and left atrium of the heart, the expressions of AM mRNA and protein were increased in the middle to late phase (5–21 days) of HHE, whereas in the brain and lung they were increased much earlier (0.5–5 days). In situ hybridization and immunohistochemistry showed AM mRNA and protein staining to be more intense in the RV in animals in the middle to late phase of HHE exposure than in the controls. During HHE, these changes in AM synthesis, which occurred strongly in the RV, occurred alongside the increase in PAP. Conceivably, AM may play a role in modulating pulmonary hypertension in HHE.

Effect of selective embolization of various sized pulmonary arteries in dogs

1963 ◽  
Vol 204 (4) ◽  
pp. 619-625 ◽  
Author(s):  
John W. Hyland ◽  
George T. Smith ◽  
Lockhart B. McGuire ◽  
Donald C. Harrison ◽  
Florence W. Haynes ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Pulmonary Arteries ◽  
Internal Diameter ◽  
Polystyrene Spheres ◽  
Selective Embolization ◽  
Blood Clots ◽  
Pulmonary Arterial ◽  
The Right

Pulmonary embolism was produced in 30 closed-chest 8-kg dogs with polystyrene spheres, glass beads, or blood clots of precise graded size. The sizes matched selectively the internal diameter of pulmonary arteries from lobar branches (5–6 mm) down to atrial arteries (0.17 mm). Emboli were injected into the right atrium until the pressure in the pulmonary artery rose 5–10 mm Hg. The number of emboli of a given size required to produce this incipient pulmonary hypertension was compared with the number of vessels of that same size as determined from the literature as well as by postmortem injection with Schlesinger mass. The number of emboli bore a constant relation to the number of vessels of that same size. With each size, the majority of vessels had to be occluded before pulmonary hypertension appeared. This was true even in the absence of anesthesia. The results support the thesis that mechanical blockade rather than vasoconstriction is the mechanism by which pulmonary hypertension is produced by emboli occluding pulmonary arterial (as opposed to arteriolar) vessels.

scholarly journals Pulmonary vessel casting in a rat model of monocrotaline-mediated pulmonary hypertension

2020 ◽  
Vol 10 (3) ◽  
pp. 204589402092212
Author(s):  
Zhongkai Zhu ◽  
Yifan Wang ◽  
Amy Long ◽  
Tianyu Feng ◽  
Maria Ocampo ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Rat Model ◽  
Vascular System ◽  
Pulmonary Arteries ◽  
Pulmonary Vasculature ◽  
Control Group ◽  
Wall Thickening ◽  
Arterial Remodeling ◽  
Pulmonary Vessel ◽  
Pulmonary Arterial

Pulmonary hypertension is a chronic vascular disease characterized by pulmonary vasoconstriction and pulmonary arterial remodeling. Pulmonary arterial remodeling is mainly due to small pulmonary arterial wall thickening and lumen occlusion. Previous studies have described intravascular changes in lung sections using histopathology, but few were able to obtain a fine detailed image of the pulmonary vascular system. In this study, we used Microfil compounds to cast the pulmonary arteries in a rat model of monocrotaline-induced pulmonary hypertension. High-quality images that enabled quantification of distal pulmonary arterial branching based on the number of vessel bifurcations/junctions were demonstrated in this model. The branch and junction counts of distal pulmonary arteries significantly decreased in the monocrotaline group compared to the control group, and this effect was inversely proportional to the mean pulmonary artery pressure observed in each group. The patterns of pulmonary vasculature and the methods for pulmonary vessel casting are presented to provide a basis for future studies of pulmonary arterial remodeling due to pulmonary hypertension and other lung diseases that involve the remodeling of vasculature.

scholarly journals The isobaric pulmonary arterial compliance in pulmonary hypertension

2021 ◽  
pp. 00941-2020
Author(s):  
Denis Chemla ◽  
Emmanuelle Berthelot ◽  
Jason Weatherald ◽  
Edmund M. T. Lau ◽  
Laurent Savale ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Arterial Compliance ◽  
Pulmonary Arteries ◽  
Right Heart ◽  
Right Heart Catheterisation ◽  
Strain Behaviour ◽  
Arterial Load ◽  
Pulmonary Arterial ◽  
Vascular Beds ◽  
The Right

Pulmonary hypertension (PH) is associated with stiffening of pulmonary arteries which increases right ventricular pulsatile loading. High pulmonary artery wedge pressure (PAWP) in postcapillary PH (Pc-PH) further decreases PA compliance (PAC) at a given pulmonary vascular resistance (PVR) compared to precapillary PH, thus responsible for a higher total arterial load. In all other vascular beds, arterial compliance is considered as mainly determined by the distending pressure, due to non-linear stress-strain behaviour of arteries. We tested the applicability, advantages and drawbacks of two comparison methods of PAC depending on the level of mean PA pressure mPAP (isobaric PAC) or PVR.Right heart catheterisation data including PAC (stroke volume/pulse pressure) were obtained in 112Pc-PH (of whom 61 had combined postcapillary and precapillary PH) and 719 idiopathic pulmonary arterial hypertension (iPAH).PAC could be compared over the same mPAP range (25–66 mmHg) in 792/831 patients (95.3%) and over the same PVR range (3–10.7 WU) in only 520/831 patients (62.6%). The main assumption underlying comparisons at a given PVR was not verified as the PVR×PAC product (RC-time) was not constant but on the contrary more variable than mPAP. In the 788/831 (94.8%) patients studied over the same PAC range (0.62–6.5 mL·mmHg−1), PVR and thus total arterial load tended to be higher in iPAH.Our study favours comparing PAC at fixed mPAP level (isobaric PAC) rather than at fixed PVR. A reappraisal of the effects of PAWP on the pulsatile and total arterial load put on the right heart is needed, and this point deserves further studies.

Exaggerated hypoxic pulmonary hypertension in endothelin B receptor-deficient rats

2002 ◽  
Vol 282 (4) ◽  
pp. L703-L712 ◽  
Author(s):  
D. Dunbar Ivy ◽  
Masashi Yanagisawa ◽  
Cheryl E. Gariepy ◽  
Sarah A. Gebb ◽  
Kelley L. Colvin ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Pressure ◽  
Protective Role ◽  
Pulmonary Vasculature ◽  
Pulmonary Resistance ◽  
Hypoxic Pulmonary Hypertension ◽  
Chronic Pulmonary Hypertension ◽  
Pulmonary Arterial ◽  
Endothelin B ◽  
Nitric Oxide Metabolites

Mechanisms by which endothelin (ET)-1 mediates chronic pulmonary hypertension remain incompletely understood. Although activation of the ET type A (ETA) receptor causes vasoconstriction, stimulation of ET type B (ETB) receptors can elicit vasodilation or vasoconstriction. We hypothesized that the ETB receptor attenuates the development of hypoxic pulmonary hypertension and studied a genetic rat model of ETB receptor deficiency (transgenic sl/sl). After 3 wk of severe hypoxia, the transgenic sl/sl pulmonary vasculature lacked expression of mRNA for the ETB receptor and developed exaggerated pulmonary hypertension that was characterized by elevated pulmonary arterial pressure, diminished cardiac output, and increased total pulmonary resistance. Plasma ET-1 was fivefold higher in transgenic sl/sl rats than in transgenic controls. Although mRNA for prepro-ET-1 was not different, mRNA for ET-converting enzyme-1 was higher in transgenic sl/sl than in transgenic control lungs. Hypertensive lungs of sl/sl rats also produced less nitric oxide metabolites and 6-ketoprostaglandin F1α, a metabolite of prostacyclin, than transgenic controls. These findings suggest that the ETB receptor plays a protective role in the pulmonary hypertensive response to chronic hypoxia.

scholarly journals Pulmonary hypertension

2016 ◽  
Vol 25 (139) ◽  
pp. 4-11 ◽  
Author(s):  
Anton Vonk Noordegraaf ◽  
Joanne A. Groeneveldt ◽  
Harm Jan Bogaard
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Combination Therapy ◽  
Review Article ◽  
Pulmonary Vasculature ◽  
Distant Future ◽  
European Guidelines ◽  
Enormous Amount ◽  
Pulmonary Arterial ◽  
The Right

In 2015, more than 800 papers were published in the field of pulmonary hypertension. A Clinical Year in Review article cannot possibly incorporate all this work and needs to be selective. The recently published European guidelines for the diagnosis and treatment of pulmonary hypertension contain an inclusive summary of all published clinical studies conducted until very recently. Here, we provide an overview of papers published after the finalisation of the guideline. In addition, we summarise recent advances in pulmonary vasculature science. The selection we made from the enormous amount of published work undoubtedly reflects our personal views and may not include all papers with a significant impact in the near or more distant future. The focus of this paper is on the diagnosis of pulmonary arterial hypertension, understanding the success of combination therapy on the right ventricle and scientific breakthroughs.

Exercise training improves lung gas exchange and attenuates acute hypoxic pulmonary hypertension but does not prevent pulmonary hypertension of prolonged hypoxia

2006 ◽  
Vol 100 (1) ◽  
pp. 20-25 ◽  
Author(s):  
Fabrice Favret ◽  
Kyle K. Henderson ◽  
Julie Allen ◽  
Jean-Paul Richalet ◽  
Norberto C. Gonzalez
Keyword(s):  
Pulmonary Hypertension ◽  
Cardiac Output ◽  
Gas Exchange ◽  
Exercise Training ◽  
Right Ventricular ◽  
Acute Hypoxia ◽  
Male Rats ◽  
Hypoxic Pulmonary Hypertension ◽  
Ventricular Afterload ◽  
Pulmonary Arterial

Our laboratory has previously shown an attenuation of hypoxic pulmonary hypertension by exercise training (ET) (Henderson KK, Clancy RL, and Gonzalez NC. J Appl Physiol 90: 2057–2062, 2001), although the mechanism was not determined. The present study examined the effect of ET on the pulmonary arterial pressure (Pap) response of rats to short- and long-term hypoxia. After 3 wk of treadmill training, male rats were divided into two groups: one (HT) was placed in hypobaric hypoxia (380 Torr); the second remained in normoxia (NT). Both groups continued to train in normoxia for 10 days, after which they were studied at rest and during hypoxic and normoxic exercise. Sedentary normoxic (NS) and hypoxic (HS) littermates were exposed to the same environments as their trained counterparts. Resting and exercise hypoxic arterial Po2 were higher in NT and HT than in NS and HS, respectively, although alveolar ventilation of trained rats was not higher. Lower alveolar-arterial Po2 difference and higher effective lung diffusing capacity for O2 in NT vs. NS and in HT vs. HS suggest ET improved efficacy of gas exchange. Pap and Pap/cardiac output were lower in NT than NS in hypoxia, indicating that ET attenuates the initial vasoconstriction of hypoxia. However, ET had no effect on chronic hypoxic pulmonary hypertension: Pap and Pap/cardiac output in hypoxia were similar in HS vs HT. However, right ventricular weight was lower in HT than in HS, although Pap was not different. Because ET attenuates the initial pulmonary vasoconstriction of hypoxia, development of pulmonary hypertension may be delayed in HT rats, and the time during which right ventricular afterload is elevated may be shorter in this group. ET effects may improve the response to acute hypoxia by increasing efficacy of gas exchange and lowering right ventricular work.

Effect of dietary fish oil on lung lipid profile and hypoxic pulmonary hypertension

1989 ◽  
Vol 66 (4) ◽  
pp. 1662-1673 ◽  
Author(s):  
S. L. Archer ◽  
G. J. Johnson ◽  
R. L. Gebhard ◽  
W. L. Castleman ◽  
A. S. Levine ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Fish Oil ◽  
Chronic Hypoxia ◽  
Corn Oil ◽  
Pulmonary Arteries ◽  
Hypoxic Pulmonary Hypertension ◽  
Dietary Fish ◽  
Lung Lipid ◽  
Pulmonary Arterial ◽  
Fish Oil Diet

The effects of dietary polyunsaturated fats on chronic hypoxic pulmonary hypertension were assessed in rats fed fish oil, corn oil, or a lower fat, “high-carbohydrate” diet (regular) beginning 1 mo before the start of hypoxia (0.4 atm, n = 30 for each). Mean pulmonary arterial pressures were lower in the chronically hypoxic rats fed fish oil (19.7 +/- 1.8 mm Hg) than in the rats fed corn oil (25.3 +/- 1.6 mm Hg) or regular diets (27.5 +/- 1.5 mm Hg, P less than 0.05). The fish oil diet increased lung eicosapentaenoic acid 50-fold and depleted lung arachidonic acid 60% (P less than 0.0001 for each). Lung thromboxane B2 and 6-ketoprostaglandin F1 alpha levels were lower, and platelet aggregation, in response to collagen, was reduced in rats fed fish oil. Chronically hypoxic rats fed fish oil had lower mortality rates than the other hypoxic rats. They also had lower blood viscosity, as well as less right ventricular hypertrophy and less peripheral extension of vascular smooth muscle to intra-acinar pulmonary arteries (P less than 0.05 for each). The mechanism by which dietary fish oil decreases pulmonary hypertension and vascular remodeling during chronic hypoxia remains uncertain. The finding that a fish oil diet can reduce the hemodynamic and morphological sequelae of chronic hypoxia may have therapeutic significance.

scholarly journals Functional and molecular factors associated with TAPSE in hypoxic pulmonary hypertension

2016 ◽  
Vol 311 (1) ◽  
pp. L59-L73 ◽  
Author(s):  
Slaven Crnkovic ◽  
Albrecht Schmidt ◽  
Bakytbek Egemnazarov ◽  
Jochen Wilhelm ◽  
Leigh M. Marsh ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Plasma Levels ◽  
Molecular Mechanisms ◽  
Chronic Hypoxia ◽  
Systolic Function ◽  
Hypoxic Pulmonary Hypertension ◽  
Interleukin 22 ◽  
Pulmonary Arterial ◽  
The Right ◽  
And Function

Adaptation of the right ventricle (RV) to increased afterload is crucial for survival in pulmonary hypertension (PH), but it is challenging to assess RV function and identify associated molecular mechanisms. The aim of the current study was to analyze the relationship between invasive and noninvasive parameters of RV morphology and function and associated molecular changes. The response of mice to normobaric hypoxia was assessed by hechocardiography, invasive hemodynamics, and histological and molecular analyses. Plasma levels of possibly novel markers of RV remodeling were measured by ELISA in patients with idiopathic pulmonary arterial hypertension (IPAH) and matched healthy controls. Chronic hypoxia-induced PH was accompanied by significantly decreased tricuspid annular plane systolic excursion (TAPSE) and unchanged RV contractility index and tau. RV hypertrophy was present without an increase in fibrosis. There was no change in α- and β-major histocompatibility class or natriuretic peptides expression. Comparative microarray analysis identified two soluble factors, fibroblast growth factor-5 (FGF5) and interleukin-22 receptor alpha-2 (IL22RA2), as being possibly associated with RV remodeling. We observed significantly higher plasma levels of IL22RA2, but not FGF5, in patients with IPAH. Hypoxic pulmonary hypertension in a stage of RV remodeling with preserved systolic function is associated with decreased pulmonary vascular compliance, mild diastolic RV dysfunction, and significant decrease in TAPSE. Subtle gene expression changes in the RV vs. the left ventricle upon chronic hypoxia suggest that the majority of changes are due to hypoxia and not due to changes in afterload. Increased IL22RA2 levels might represent a novel RV adaptive mechanism.

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