C-type natriuretic peptide expression and pulmonary vasodilation in hypoxia-adapted rats

1998 ◽  
Vol 275 (4) ◽  
pp. L645-L652 ◽  
Author(s):  
James R. Klinger ◽  
Farjaad M. Siddiq ◽  
Richard A. Swift ◽  
Cynthia Jackson ◽  
Linda Pietras ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricle ◽  
Natriuretic Peptide ◽  
Right Atrium ◽  
Chronic Hypoxia ◽  
Right Atrial ◽  
Mrna Levels ◽  
Hypoxic Pulmonary Hypertension ◽  
Pulmonary Arterial ◽  
The Right

Atrial and brain natriuretic peptides (ANP and BNP, respectively) are potent pulmonary vasodilators that are upregulated in hypoxia-adapted rats and may protect against hypoxic pulmonary hypertension. To test the hypothesis that C-type natriuretic peptide (CNP) also modulates pulmonary vascular responses to hypoxia, we compared the vasodilator effect of CNP with that of ANP on pulmonary arterial rings, thoracic aortic rings, and isolated perfused lungs obtained from normoxic and hypoxia-adapted rats. We also measured CNP and ANP levels in heart, lung, brain, and plasma in normoxic and hypoxia-adapted rats. Steady-state CNP mRNA levels were quantified in the same organs by relative RT-PCR. CNP was a less potent vasodilator than ANP in preconstricted thoracic aortic and pulmonary arterial rings and in isolated lungs from normoxic and hypoxia-adapted rats. Chronic hypoxia increased plasma CNP (15 ± 2 vs. 6 ± 1 pg/ml; P < 0.05) and decreased CNP in the right atrium (35 ± 14 vs. 65 ± 17 pg/mg protein; P < 0.05) and in the lung (3 ± 1 vs. 14 ± 3 pg/mg protein; P < 0.05) but had no effect on CNP in brain or right ventricle. Chronic hypoxia increased ANP levels fivefold in the right ventricle (49 ± 5 vs. 11 ± 2 pg/mg protein; P < 0.05) but had no effect on ANP in lung or brain. There was a trend toward decreased ANP levels in the right atrium (2,009 ± 323 vs. 2,934 ± 397 pg/mg protein; P = not significant). No differences in CNP transcript levels were observed between the two groups of rats except that the right atrial CNP mRNA levels were lower in hypoxia-adapted rats. We conclude that CNP is a less potent pulmonary vasodilator than ANP in normoxic and hypoxia-adapted rats and that hypoxia raises circulating CNP levels without increasing cardiopulmonary CNP expression. These findings suggest that CNP may be less important than ANP or BNP in protecting against hypoxic pulmonary hypertension in rats.

Cardiac modulations of ANG II receptor expression in rats with hypoxic pulmonary hypertension

2002 ◽  
Vol 283 (2) ◽  
pp. H733-H740 ◽  
Author(s):  
Christophe Adamy ◽  
Patricia Oliviero ◽  
Saadia Eddahibi ◽  
Lydie Rappaport ◽  
Jane-Lise Samuel ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Chronic Hypoxia ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Hypoxic Pulmonary Hypertension ◽  
Cardiac Ventricles ◽  
The Right

Right ventricular myocardial hypertrophy during hypoxic pulmonary hypertension is associated with local renin-angiotensin system activation. The expression of angiotensin II type 1 (AT1) and type 2 (AT2) receptors in this setting has never been investigated. We have therefore examined the chronic hypoxia pattern of AT1 and AT2expression in the right and left cardiac ventricles, using in situ binding and RT-PCR assays. Hypoxia produced right, but not left, ventricular hypertrophy after 7, 14, and 21 days, respectively. Hypoxia for 2 days was associated in each ventricle with a simultaneous and transient increase ( P < 0.05) in AT1 binding and AT1 mRNA levels in the absence of any significant change in AT2 expression level. Only after 14 days of hypoxia, AT2 binding increased ( P < 0.05) in the two ventricles, concomitantly with a right ventricular decrease ( P < 0.05) in AT2 mRNA. Along these data, AT1 and AT2 binding remained unchanged in both the left and hypertrophied right ventricles from rats treated with monocrotaline for 30 days. These results indicate that chronic hypoxia induces modulations of AT1 and AT2 receptors in both cardiac ventricles probably through direct and indirect mechanisms, respectively, which modulations may participate in myogenic (at the level of smooth or striated myocytes) rather than in the growth response of the heart to hypoxia.

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.

Enhanced endothelin-1 and endothelin receptor gene expression in chronic hypoxia

1994 ◽  
Vol 77 (3) ◽  
pp. 1451-1459 ◽  
Author(s):  
H. Li ◽  
S. J. Chen ◽  
Y. F. Chen ◽  
Q. C. Meng ◽  
J. Durand ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Arterial Pressure ◽  
Chronic Hypoxia ◽  
Pulmonary Arterial Pressure ◽  
Mrna Levels ◽  
Hypoxic Pulmonary Hypertension ◽  
Receptor Mrna ◽  
Etb Receptor ◽  
Pulmonary Arterial

To test the hypothesis that endothelin (ET)-1 synthesis and ET receptor levels are increased selectively in the lung of rats with chronic hypoxic pulmonary hypertension, the current study examined the effects of exposure to chronic hypoxia (10% O2, 1 atm, 4 wk) on pulmonary arterial pressure, ET-1 levels in plasma and lung, and ET-1 and ETA and ETB receptor mRNA levels in lung, heart, pulmonary artery, aorta, kidney, spleen, and liver. Hypoxic exposure was associated with increases in pulmonary arterial pressure, plasma ET-1 levels, ET-1 mRNA in lung and pulmonary artery, and ET-1 stores and ETA and ETB receptor mRNA levels in lung. In thoracic aorta and the four heart chambers, ETA and ETB receptor mRNA levels were increased, but ET-1 mRNA levels were unchanged from air control levels. No change in ET-1 or ET receptor mRNA levels was seen in organs perfused by the systemic vascular bed, except in liver, where ETA receptor mRNA levels were decreased. The findings of concomitant increases in gene transcript levels for ET-1 and the ETA and ETB receptors in lung, but not in the great vessels or any other organ examined, are consistent with the hypothesis that increased ET-1 synthesis in the lung contributes to pulmonary vascular remodeling and the maintenance of chronic hypoxic pulmonary hypertension.

scholarly journals P686 Right atrial, right ventricular and pulmonary cement embolism: a rare complication of percutaneous vertebroplasty

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
S Akhunova ◽  
R Khayrullin ◽  
N Stekolshchikova ◽  
M Samigullin ◽  
V Padiryakov
Keyword(s):  
Pulmonary Artery ◽  
Right Ventricle ◽  
Right Atrium ◽  
Percutaneous Vertebroplasty ◽  
Rare Complication ◽  
Clinical Manifestations ◽  
Stable Condition ◽  
Right Atrial ◽  
Cement Embolism ◽  
The Right

Abstract A 68-year-old man was admitted to the hospital with complaints of pain in the lumbar spine. He had L5 disc herniation, Spinal stenosis of the L5 root canal - S1 on the right in the past medical history. Percutaneous vertebroplasty at the level of L3 and Th8 vertebral bodies was performed six months ago due to painful vertebral hemangioma. The man is suffering from arterial hypertension, receives antihypertensive therapy. During routine transthoracic echocardiography, a hyperechoic structure with a size of 9.5 x 0.9 cm was found in the right atrium and right ventricle. Chest computed tomography with contrast enhancement revealed signs of bone cement in the right atrium and right ventricle, in the right upper lobe artery, in the branches of the upper lobe artery, in the paravertebral venous plexuses. Considering the duration of the disease, the stable condition, the absence of clinical manifestations and disorders of intracardiac hemodynamics, it was decided to refrain from surgical treatment. Antiplatelet therapy and dynamic observation were recommended. Conclusion Percutaneous vertebroplasty is a modern minimally invasive surgical procedure for the treatment of degenerative-dystrophic diseases of the spine. However, the cement can penetrate into the paravertebral veins and migrate to the right chambers of the heart and the pulmonary artery. This clinical case demonstrates asymptomatic cement embolism of the right chambers of the heart and pulmonary artery after percutaneous vertebroplasty, detected incidentally during routine echocardiography. Abstract P686 Figure.

scholarly journals Giant right atrial myxoma: A rare cause of cardiovascular collapse

2019 ◽  
Vol 7 ◽  
pp. 2050313X1984146
Author(s):  
Andres Beiras-Fernandez ◽  
Angela Kornberger ◽  
Hazem El-Beyrouti ◽  
Christian-Friedrich Vahl
Keyword(s):  
Heart Failure ◽  
Right Ventricle ◽  
Right Atrium ◽  
Heart Valves ◽  
Surgical Intervention ◽  
Atrial Myxoma ◽  
Right Atrial ◽  
Cardiovascular Collapse ◽  
Right Atrial Myxoma ◽  
The Right

We report the case of a patient with a giant right atrial myxoma that remained clinically silent until it almost completely obliterated the right atrium, prolapsed into the right ventricle and obstructed the tricuspid valve inflow. This case illustrates the importance of rapid surgical intervention in the setting of acute heart failure caused by tumor masses obliterating heart valves or cardiac chambers.

scholarly journals Brain natriuretic peptide inhibits hypoxic pulmonary hypertension in rats

1998 ◽  
Vol 84 (5) ◽  
pp. 1646-1652 ◽  
Author(s):  
James R. Klinger ◽  
Rod R. Warburton ◽  
Linda Pietras ◽  
Nicholas S. Hill
Keyword(s):  
Pulmonary Hypertension ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Systolic Pressure ◽  
High Rate ◽  
Hypoxic Pulmonary Hypertension ◽  
Ventricular Systolic Pressure ◽  
Hypoxic Conditions ◽  
Pulmonary Vasodilator ◽  
The Right

Brain natriuretic peptide (BNP) is a pulmonary vasodilator that is elevated in the right heart and plasma of hypoxia-adapted rats. To test the hypothesis that BNP protects against hypoxic pulmonary hypertension, we measured right ventricular systolic pressure (RVSP), right ventricle (RV) weight-to-body weight (BW) ratio (RV/BW), and percent muscularization of peripheral pulmonary vessels (%MPPV) in rats given an intravenous infusion of BNP, atrial natriuretic peptide (ANP), or saline alone after 2 wk of normoxia or hypobaric hypoxia (0.5 atm). Hypoxia-adapted rats had higher hematocrits, RVSP, RV/BW, and %MPPV than did normoxic controls. Under normoxic conditions, BNP infusion (0.2 and 1.4 μg/h) increased plasma BNP but had no effect on RVSP, RV/BW, or %MPPV. Under hypoxic conditions, low-rate BNP infusion (0.2 μg/h) had no effect on plasma BNP or on severity of pulmonary hypertension. However, high-rate BNP infusion (1.4 μg/h) increased plasma BNP (69 ± 8 vs. 35 ± 4 pg/ml, P < 0.05), lowered RV/BW (0.87 ± 0.05 vs. 1.02 ± 0.04, P < 0.05), and decreased %MPPV (60 vs. 74%, P < 0.05). There was also a trend toward lower RVSP (55 ± 3 vs. 64 ± 2, P = not significant). Infusion of ANP at 1.4 μg/h increased plasma ANP in hypoxic rats (759 ± 153 vs. 393 ± 54 pg/ml, P < 0.05) but had no effect on RVSP, RV/BW, or %MPPV. We conclude that BNP may regulate pulmonary vascular responses to hypoxia and, at the doses used in this study, is more effective than ANP at blunting pulmonary hypertension during the first 2 wk of hypoxia.

scholarly journals MAP kinase kinase kinase-2 (MEKK2) regulates hypertrophic remodeling of the right ventricle in hypoxia-induced pulmonary hypertension

2013 ◽  
Vol 304 (2) ◽  
pp. H269-H281 ◽  
Author(s):  
R. Dale Brown ◽  
S. Kelly Ambler ◽  
Min Li ◽  
Timothy M. Sullivan ◽  
Lauren N. Henry ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pulmonary Hypertension ◽  
Right Ventricle ◽  
Cardiac Myocyte ◽  
Chronic Hypoxia ◽  
Regulatory Protein ◽  
Right Heart Failure ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
The Right

Pulmonary hypertension (PH) results in pressure overload of the right ventricle (RV) of the heart, initiating pathological RV remodeling and ultimately leading to right heart failure. Substantial research indicates that signaling through the MAPK superfamily mediates pathological cardiac remodeling. These considerations led us to test the hypothesis that the regulatory protein MAPKKK-2 (MEKK2) contributes to RV hypertrophy in hypoxia-induced PH. Transgenic mice with global knockout of MEKK2 (MEKK2−/− mice) and age-matched wild-type (WT) mice were exposed to chronic hypobaric hypoxia (10% O2, 6 wk) and compared with animals under normoxia. Exposure to chronic hypoxia induced PH in WT and MEKK2−/− mice. In response to PH, WT mice showed RV hypertrophy, demonstrated as increased ratio of RV weight to body weight, increased RV wall thickness at diastole, and increased cardiac myocyte size compared with normoxic control animals. In contrast, each of these measures of RV hypertrophy seen in WT mice after chronic hypoxia was attenuated in MEKK2−/− mice. Furthermore, chronic hypoxia elicited altered programs of hypertrophic and inflammatory gene expression consistent with pathological RV remodeling in WT mice; MEKK2 deletion selectively inhibited inflammatory gene expression compared with WT mice. The actions of MEKK2 were mediated in part through regulation of the abundance and phosphorylation of its effector, ERK5. In conclusion, signaling by MEKK2 contributes to RV hypertrophy and altered myocardial inflammatory gene expression in response to hypoxia-induced PH. Therapies targeting MEKK2 may protect the myocardium from hypertrophy and pathological remodeling in human PH.

Tricuspid valve relocation with endomyocardial fibrosis removal for Löeffler’s endocarditis

2019 ◽  
Vol 56 (3) ◽  
pp. 622-624
Author(s):  
Tohru Asai ◽  
Fumihiro Miyashita ◽  
Hiromitsu Nota ◽  
Piers N Vigers
Keyword(s):  
Heart Failure ◽  
Right Ventricle ◽  
Right Atrium ◽  
Hypereosinophilic Syndrome ◽  
Right Heart Failure ◽  
Right Atrial ◽  
Endomyocardial Fibrosis ◽  
Right Heart ◽  
Atrial Enlargement ◽  
The Right

Abstract Löffler endocarditis with hypereosinophilic syndrome is rare but can cause critical ventricular obliteration by endomyocardial fibrosis. A 52-year-old woman experienced severe right heart failure with extreme shrinkage of her right ventricle, severe tricuspid regurgitation and marked right atrial enlargement. Preoperative tests showed identical pressures in the right atrium and pulmonary artery. Endocardial stripping was done, and to enlarge the right ventricle, we relocated the anterior and posterior tricuspid leaflets cephalad, up the right atrium wall, to ‘ventricularize’ a portion of the right atrium, with autologous pericardial augmentation of the tricuspid leaflets. An annuloplasty ring was added to reinforce the relocated tricuspid attachment. Right heart pressures normalized postoperatively. The patient recovered uneventfully. She has received corticosteroid therapy continuously and has shown no recurrence of heart failure in the 5 years since surgery.

Cellular adaptation during chronic neonatal hypoxic pulmonary hypertension

1991 ◽  
Vol 261 (4) ◽  
pp. L97-L104 ◽  
Author(s):  
Kurt R. Stenmark ◽  
Almas A. Aldashev ◽  
Ernest C. Orton ◽  
A. G. Durmowicz ◽  
D. B. Badesch ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Arterial Wall ◽  
Chronic Hypoxia ◽  
Left Pulmonary Artery ◽  
Right Atrial ◽  
Vascular Changes ◽  
Hypoxic Pulmonary Hypertension

Newbor animals develop more severe hypoxic pulmonary hypertension than do adults, their vascular changes are greater, and both the hypertension and vascular changes occur more rapidly. We hypothesize that this differential developmentally controlled response may arise from either a difference in the type or quantity of endogenously secreted mediators in response to a given injury or a difference in the replicative and/or matrix-producing response of the vascular cells to physical or chemical stimuli. We investigated the effect of chronic hypoxia (14 days) on the proliferative and matrix-producing phenotype of the neonatal (14-day-old) pulmonary artery smooth muscle cell (SMC) and examined the heterogeneity and potential mechanisms responsible for this response. In situ hybridization studies demonstrated a remarkable change in the distribution of cells hybridizing with a tropoelastin cRNA probe after 14 days of hypoxia. Studies also demonstrated a population of SMC that did not hybridize with the elastin or collagen probes, indicating that the pulmonary artery contains SMC of multiple phenotypes and that the response to hypoxic and hemodynamic stress is not uniform for the various types. Bromodeoxyuridine labeling experiments indicated a large increase in DNA synthesis in hypertensive vessels, which, again, was not uniform either across or along the arterial wall. In vitro experiments with neonatal SMC suggested that hypoxia alone could not be responsible for the proliferative or matrix changes. These observations were supported by in vivo experiments in which coarctation of the left pulmonary artery, which markedly decreased pressure and flow to the left lung in hypoxic animals (14 days), resulted in significant decreases in collagen and elastin message levels in the left pulmonary artery distal to the coarctation compared with location-matched vessels from the right lung. Finally, we noted marked decreases in B-receptor density and adenyl cyclase activity in right atrial and pulmonary artery tissue from the chronically hypoxic animals. Decreases in the ability of the cell to produce adenosine 3',5'-cyclic monophosphate could significantly affect both the proliferative and matrix-producing potential of the SMC. We conclude that in vivo adaptation of the pulmonary artery SMC to chronic hypoxia includes changes in protein synthesis, cell proliferation, receptor expression, and enzyme activity. Further, there is a marked heterogeneity of these responses both across and along the arterial wall. hypoxia; phenotype; signal transductions; smooth muscle cells

Sign in / Sign up

Export Citation Format

Share Document