Abstract 17280: A New in vivo Imaging Protocol for Non-Invasive Detection of Right Ventricular Dysfunction in a Pulmonary Hypertension Mouse Model

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Thomas Hansen ◽  
Kristen Bubb ◽  
Gemma Figtree
Keyword(s):  
Pulmonary Hypertension ◽  
Mouse Model ◽  
Right Ventricular ◽  
Systolic Pressure ◽  
Saline Control ◽  
Novel Therapies ◽  
Imaging Protocol ◽  
Non Invasive ◽  
Rv Function

Introduction: Accurate measurements of right ventricular (RV) function are critical for studying novel therapies impacting the heart and pulmonary circulation. Until now, assessment in mouse models has relied on invasive measures. Improvements in mouse echocardiography may facilitate application of measures recently validated in humans, including tricuspid annular plane systolic excursion (TAPSE) and RV-S’ (systolic excursion velocity), to allow non-invasive assessment of RV function. Aims: To apply and validate TAPSE and RV-S’ using high-resolution echocardiography for the measurement of RV function in a mouse model of pulmonary hypertension (PH). Methods: Echocardiography was performed on mice 3 weeks after induction of PH using inhaled bleomycin or saline control. PAT, TAPSE and RV-S’ were recorded in mice using a 55-mHz transducer (Visualsonics, Vevo3100). Invasive measurements of right ventricular systolic pressure (RVSP) were obtained via catheterisation of the internal jugular vein, prior to culling. Results: RVSP was significantly elevated in bleomycin-treated mice ( 33.41±0.8mmHg n=10) compared to controls ( 25.66±0.9mmHg n=11; p<0.0001). Similarly, RV hypertrophy was observed in bleomycin mice [RV:body weight 1.156±0.03g/kg n=11] compared with control ( 0.968±0.02g/kg n=12; p=0.0002). TAPSE was sensitive to these differences, being significantly reduced in bleomycin mice ( 0.5739±0.020mm n=8) compared with control ( 0.7387±0.033mm n=10; p=0.0012), and correlated significantly with invasive RVSP (r 2 =0.7218; p<0.0001). RV-S’ was also reduced in bleomycin mice (18.14±0.98mm/s n=7) compared with control (25.38±1.24mm/s n=8; p=0.0006) and correlated strongly with RVSP (r 2 =0.6378; p=0.0011). The correlation of both TAPSE and RV-S’ with RVSP compared favourably to the previously used surrogate measure of RVSP in mice, PAT (r 2 =0.5278; p=0.0002). Conclusions: TAPSE and RV-S’ can be applied in mouse echocardiography, and are sensitive, non-invasive measures of PH and RV dysfunction, comparing well with gold-standard invasive right ventricular systolic pressures. This may benefit the power of future preclinical studies of novel therapies in pulmonary hypertension and RV dysfunction.

scholarly journals Delineating the molecular and histological events that govern right ventricular recovery using a novel mouse model of pulmonary artery de-banding

2019 ◽  
Vol 116 (10) ◽  
pp. 1700-1709 ◽  
Author(s):  
Mario Boehm ◽  
Xuefei Tian ◽  
Yuqiang Mao ◽  
Kenzo Ichimura ◽  
Melanie J Dufva ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Mouse Model ◽  
Pulmonary Artery ◽  
Right Ventricular ◽  
Exercise Capacity ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Sequence Of Events ◽  
Reverse Remodelling ◽  
Rv Function

Abstract Aims The temporal sequence of events underlying functional right ventricular (RV) recovery after improvement of pulmonary hypertension-associated pressure overload is unknown. We sought to establish a novel mouse model of gradual RV recovery from pressure overload and use it to delineate RV reverse-remodelling events. Methods and results Surgical pulmonary artery banding (PAB) around a 26-G needle induced RV dysfunction with increased RV pressures, reduced exercise capacity and caused liver congestion, hypertrophic, fibrotic, and vascular myocardial remodelling within 5 weeks of chronic RV pressure overload in mice. Gradual reduction of the afterload burden through PA band absorption (de-PAB)—after RV dysfunction and structural remodelling were established—initiated recovery of RV function (cardiac output and exercise capacity) along with rapid normalization in RV hypertrophy (RV/left ventricular + S and cardiomyocyte area) and RV pressures (right ventricular systolic pressure). RV fibrotic (collagen, elastic fibres, and vimentin+ fibroblasts) and vascular (capillary density) remodelling were equally reversible; however, reversal occurred at a later timepoint after de-PAB, when RV function was already completely restored. Microarray gene expression (ClariomS, Thermo Fisher Scientific, Waltham, MA, USA) along with gene ontology analyses in RV tissues revealed growth factors, immune modulators, and apoptosis mediators as major cellular components underlying functional RV recovery. Conclusion We established a novel gradual de-PAB mouse model and used it to demonstrate that established pulmonary hypertension-associated RV dysfunction is fully reversible. Mechanistically, we link functional RV improvement to hypertrophic normalization that precedes fibrotic and vascular reverse-remodelling events.

Anti-monocyte chemoattractant protein-1 gene therapy attenuates pulmonary hypertension in rats

2002 ◽  
Vol 283 (5) ◽  
pp. H2021-H2028 ◽  
Author(s):  
Yasuhiro Ikeda ◽  
Yoshikazu Yonemitsu ◽  
Chu Kataoka ◽  
Shiro Kitamoto ◽  
Terutoshi Yamaoka ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Mononuclear Cells ◽  
Systolic Pressure ◽  
Signal Pathway ◽  
Dominant Negative ◽  
Monocyte Chemoattractant Protein 1 ◽  
Ventricular Systolic Pressure

Monocyte/macrophage chemoattractant protein-1 (MCP-1), a potent chemoattractant chemokine and an activator for mononuclear cells, may play a role in the initiation and/or progression of pulmonary hypertension (PH). To determine whether blockade of a systemic MCP-1 signal pathway in vivo may prevent PH, we intramuscularly transduced a naked plasmid encoding a 7-NH2terminus-deleted dominant negative inhibitor of the MCP-1 (7ND MCP-1) gene in monocrotaline-induced PH. We also simultaneously gave a duplicate transfection at 2-wk intervals or skeletal muscle-directed in vivo electroporation (EP) to evaluate whether a longer or higher expression might be more effective. The intramuscular reporter gene expression was enhanced 10 times over that by EP than by simple injection, and a significant 7ND MCP-1 protein in plasma was detected only in the EP group. 7ND MCP-1 gene transfer significantly inhibited the progression of MCT-induced PH as evaluated by right ventricular systolic pressure, right ventricular hypertrophy, medial hypertrophy of pulumonary arterioles, and mononuclear cell infiltration into the lung. Differential effects of longer or higher transgene expression were not apparent. Although the in vivo kinetics of 7ND MCP-1 gene therapy should be studied further, these encouraging results suggest that an anti-inflammatory strategy via blockade of the MCP-1 signal pathway may be an alternative approach to treat subjects with PH.

Vascular Abnormalities and Pulmonary Hypertension in the Berkeley Sickle Mouse.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3185-3185
Author(s):  
David R. Archer ◽  
Shawn Elms ◽  
Joshua Boutwell ◽  
Jennifer Perry ◽  
Roy Sutliff
Keyword(s):  
Pulmonary Hypertension ◽  
Cardiac Output ◽  
Mean Arterial Pressure ◽  
Endothelial Dysfunction ◽  
Mouse Model ◽  
Arterial Pressure ◽  
Right Ventricular ◽  
The Mean

Abstract Clinically, pulmonary hypertension is a major risk factor for mortality in adults with sickle cell disease. Contributing factors probably include red cell hemolysis and vaso-occlusive injury with their associated oxidative and inflammatory stimuli. Previously, we have described RBC hemolysis and endothelial oxidative stress in the Berkeley sickle mouse model and extend those studies in this work to investigate cardiovascular and endothelial dysfunction. Eight to ten month old homozygous and hemizygous Berkeley sickle mice and C57BL/6 control mice were used for all aspects of these experiments. In vivo measurements of mean arterial pressure and right ventricular pressures were conducted in fully anesthetized mice using a pressure transducer inserted in the carotid and right ventricle respectively. Following in vivo readings hearts were excised for measurement of ventricular mass. The ascending aorta was removed and cut into 5 mm rings for in vitro studies of agonist- induced contractility and relaxation. The mean arterial pressure of the hemizygous sickle mice (70.6 ± 3.4) was significantly lower than the control mice (86.0 ± 3.1) and the mean arterial pressure of homozygous sickle mice (59.0 ± 2.2 mmHg) was significantly lower than the hemizygous and control mice (p≤0.05 and p≤0.001, respectively). The right ventricular pressure showed a trend that approached significance (p= 0.08) such that pressures in homozygous mice were ≥ than those in hemizygous which were ≥ than those in control mice. Increased basal cardiac output was suggested by significant left ventricular hypertrophy. In vitro examination of potassium chloride activation of voltage gated calcium channels showed no significant difference in sensitivity or maximal contraction. Similarly, there was no difference in sensitivity to the α1 agonist, phenylephrine. However, both hemi- and homozygous mice showed a significant reduction in maximal force of contraction (normalized to cross sectional area when compared to controls. Maximal acetylcholine induced relaxation of aortic rings was significantly reduced (p≤0.05) in homozygous sickle mice compared to controls. The same effect was not seen with sodium nitroprusside induced relaxation indicating that the acetylcholine effect was not due to effects on the smooth muscle but was endothelium-dependent. The Berkeley mouse model shows cardiac hypertrophy consistent with the increased cardiac output associated with chronic anemia and a reduced basal mean arterial blood pressure similar to that seen in humans. 8–10 month old mice have increased right ventricular pressure and RV mass indicative of pulmonary hypertension. Further endothelial dysfunction is characterized by a reduction in the maximal relaxation elicited by acetylcholine. Therefore, the Berkeley mouse is a good model for investigating sickle related endothelial dysfunction.

scholarly journals Right ventricular myocardial oxygen tension is reduced in monocrotaline-induced pulmonary hypertension in the rat and restored by myo-inositol trispyrophosphate

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marta Oknińska ◽  
Zuzanna Zambrowska ◽  
Karolina Zajda ◽  
Aleksandra Paterek ◽  
Klaudia Brodaczewska ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Right Ventricular ◽  
Oxygen Tension ◽  
Systolic Pressure ◽  
Wall Stress ◽  
Saline Control ◽  
Oxygen Balance ◽  
Important Target ◽  
Oxygen Dissociation

AbstractPulmonary hypertension (PH) initially results in compensatory right ventricular (RV) hypertrophy, but eventually in RV failure. This transition is poorly understood, but may be triggered by hypoxia. Measurements of RV oxygen tension (pO2) in PH are lacking. We hypothesized that RV hypoxia occurs in monocrotaline-induced PH in rats and that myo-inositol trispyrophosphate (ITPP), facilitating oxygen dissociation from hemoglobin, can relieve it. Rats received monocrotaline (PH) or saline (control) and 24 days later echocardiograms, pressure–volume loops were obtained and myocardial pO2 was measured using a fluorescent probe. In PH mean pulmonary artery pressure more than doubled (35 ± 5 vs. 15 ± 2 in control), RV was hypertrophied, though its contractility was augmented. RV and LV pO2 was 32 ± 5 and 15 ± 8 mmHg, respectively, in control rats. In PH RV pO2 was reduced to 18 ± 9 mmHg, while LV pO2 was unchanged. RV pO2 correlated with RV diastolic wall stress (negatively) and LV systolic pressure (positively). Acute ITPP administration did not affect RV or LV pO2 in control animals, but increased RV pO2 to 26 ± 5 mmHg without affecting LV pO2 in PH. RV oxygen balance is impaired in PH and as such can be an important target for PH therapy. ITPP may be one of such potential therapies.

Abstract 19288: Pulmonary Hypertension and Sex Hormone Depletion Affect Lung and Right Ventricular Estrogen Receptor Expression

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Andrea Frump ◽  
Amanda Fisher ◽  
Anthony Cucci ◽  
Marjorie Albrecht ◽  
Kara Goss ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Systolic Pressure ◽  
Receptor Expression ◽  
Female Rats ◽  
Sprague Dawley ◽  
Apoptotic Signaling ◽  
Ovx Rats ◽  
Rv Function ◽  
Er Expression

Introduction: Women with pulmonary arterial hypertension exhibit more preserved right ventricular (RV) function than men. The underlying mechanisms are unknown. We measured 17beta-estradiol (E2) levels and lung and RV expression of the two main estrogen receptors (ERalpha and -beta) in male and in intact or ovariectomized (OVX) female rats with Su5416/hypoxia (SuHx)-induced pulmonary hypertension (PH). Hypothesis: E2 is required for adaptation to increased RV afterload in females, and ER expression is inversely correlated with PH severity. Methods: Male and age-matched female Sprague-Dawley rats received Su5416 (20mg/kg), followed by 3 weeks of hypoxia (Patm=362 mmHg) and 4 weeks of room air. Selected females underwent OVX with or without concomitant E2 repletion (75 mcg/kg/d). RV hypertrophy (RV/[LV+S]), RV systolic pressure (RVSP), and PA muscularization were measured; complemented by echocardiographic assessment of RV function and measurement of exercise capacity (VO2max). In addition, we assessed RV pro-apoptotic signaling (bcl-2/bax; caspase-3 activity), serum E2 levels, and lung and RV ER expression by Western blot. N was 7-8/group. P<0.05 was considered significant. Results: While no sex differences were noted in RV/(LV+S), RVSP or PA remodeling, female SuHx rats exhibited more preserved cardiac indices (CI; p<0.05). OVX worsened SuHx-induced alterations in RV hypertrophy, RVSP and CI (p<0.05). In turn, E2 replacement in SuHx-OVX rats prevented SuHx-induced alterations in PH endpoints and RV function; this was accompanied by attenuated RV pro-apoptotic signaling. RV ERbeta decreased in OVX SuHx females, but was restored with E2 repletion (p<0.05). RV ERbeta correlated negatively with RVSP and RV/(LV+S), and positively with RV bcl-2/bax (p<0.05). Similarly, serum E2 levels correlated negatively with RVSP and RV/(LV+S) (p<0.05). While healthy females exhibited higher lung ERbeta than healthy males (p<0.05), no such differences were observed in SuHx-PH. Neither lung nor RV ERalpha was affected by PH or hormone depletion. Conclusions: E2 is required for female adaption to SuHx-PH, through a mechanism that may involve ERbeta-mediated RV cell viability signaling, thus allowing for better adaptation to increases in RV afterload.

scholarly journals Right ventricular outflow tract velocity time integral-to-pulmonary artery systolic pressure ratio: a non-invasive metric of pulmonary arterial compliance differs across the spectrum of pulmonary hypertension

2019 ◽  
Vol 9 (2) ◽  
pp. 204589401984197 ◽  
Author(s):  
Priyanka T. Bhattacharya ◽  
Gregory S. Troutman ◽  
Frances Mao ◽  
Arieh L. Fox ◽  
Monique S. Tanna ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Functional Capacity ◽  
Arterial Compliance ◽  
Systolic Pressure ◽  
Outflow Tract ◽  
Velocity Time Integral ◽  
Non Invasive ◽  
Time Integral ◽  
Pulmonary Arterial

Pulmonary arterial compliance (PAC), invasively assessed by the ratio of stroke volume to pulmonary arterial (PA) pulse pressure, is a sensitive marker of right ventricular (RV)-PA coupling that differs across the spectrum of pulmonary hypertension (PH) and is predictive of outcomes. We assessed whether the echocardiographically derived ratio of RV outflow tract velocity time integral to PA systolic pressure (RVOT-VTI/PASP) (a) correlates with invasive PAC, (b) discriminates heart failure with preserved ejection-associated PH (HFpEF-PH) from pulmonary arterial hypertension (PAH), and (c) is associated with functional capacity. We performed a retrospective cohort study of patients with PAH (n = 70) and HFpEF-PH (n = 86), which was further dichotomized by diastolic pressure gradient (DPG) into isolated post-capillary PH (DPG < 7 mmHg; Ipc-PH, n = 54), and combined post- and pre-capillary PH (DPG ≥ 7 mm Hg; Cpc-PH, n = 32). Of the 156 patients, 146 had measurable RVOT-VTI or PASP and were included in further analysis. RVOT-VTI/PASP correlated with invasive PAC overall (ρ = 0.61, P < 0.001) and for the PAH (ρ = 0.38, P = 0.002) and HFpEF-PH (ρ = 0.63, P < 0.001) groups individually. RVOT-VTI/PASP differed significantly across the PH spectrum (PAH: 0.13 [0.010–0.25] vs. Cpc-PH: 0.20 [0.12–0.25] vs. Ipc-PH: 0.35 [0.22–0.44]; P < 0.001), distinguished HFpEF-PH from PAH (AUC = 0.72, 95% CI = 0.63–0.81) and Cpc-PH from Ipc-PH (AUC = 0.78, 95% CI = 0.68–0.88), and remained independently predictive of 6-min walk distance after multivariate analysis (standardized β-coefficient = 27.7, 95% CI = 9.2–46.3; P = 0.004). Echocardiographic RVOT-VTI/PASP is a novel non-invasive metric of PAC that differs across the spectrum of PH. It distinguishes the degree of pre-capillary disease within HFpEF-PH and is predictive of functional capacity.

scholarly journals Estradiol improves right ventricular function in rats with severe angioproliferative pulmonary hypertension: effects of endogenous and exogenous sex hormones

2015 ◽  
Vol 308 (9) ◽  
pp. L873-L890 ◽  
Author(s):  
Andrea L. Frump ◽  
Kara N. Goss ◽  
Alexandra Vayl ◽  
Marjorie Albrecht ◽  
Amanda Fisher ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Proinflammatory Cytokine ◽  
Systolic Pressure ◽  
Sprague Dawley ◽  
Mediated Effects ◽  
Ovx Rats ◽  
Sprague Dawley Rats ◽  
Estrogen Effects ◽  
Rv Function

Estrogens are disease modifiers in PAH. Even though female patients exhibit better right ventricular (RV) function than men, estrogen effects on RV function (a major determinant of survival in PAH) are incompletely characterized. We sought to determine whether sex differences exist in RV function in the SuHx model of PAH, whether hormone depletion in females worsens RV function, and whether E2 repletion improves RV adaptation. Furthermore, we studied the contribution of ERs in mediating E2’s RV effects. SuHx-induced pulmonary hypertension (SuHx-PH) was induced in male and female Sprague-Dawley rats as well as OVX females with or without concomitant E2 repletion (75 μg·kg−1·day−1). Female SuHx rats exhibited superior CI than SuHx males. OVX worsened SuHx-induced decreases in CI and SuHx-induced increases in RVH and inflammation (MCP-1 and IL-6). E2 repletion in OVX rats attenuated SuHx-induced increases in RV systolic pressure (RVSP), RVH, and pulmonary artery remodeling and improved CI and exercise capacity (V̇o2max). Furthermore, E2 repletion ameliorated SuHx-induced alterations in RV glutathione activation, proapoptotic signaling, cytoplasmic glycolysis, and proinflammatory cytokine expression. Expression of ERα in RV was decreased in SuHx-OVX but was restored upon E2 repletion. RV ERα expression was inversely correlated with RVSP and RVH and positively correlated with CO and apelin RNA levels. RV-protective E2 effects observed in females were recapitulated in male SuHx rats treated with E2 or with pharmacological ERα or ERβ agonists. Our data suggest significant RV-protective ER-mediated effects of E2 in a model of severe PH.

Right ventricular pressure-volume loop shape and systolic pressure change in pulmonary hypertension

2021 ◽  
Author(s):  
Manuel Jonas Richter ◽  
Steven Hsu ◽  
Athiththan Yogeswaran ◽  
Faeq Husain-Syed ◽  
István Vadász ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Pulse Pressure ◽  
Augmentation Index ◽  
Systolic Pressure ◽  
Pressure Differential ◽  
Stroke Work ◽  
Loop Shape ◽  
Pulmonary Arterial ◽  
Rv Function

Right ventricular (RV) function determines outcome in pulmonary arterial hypertension (PAH). RV pressure-volume loops - the gold standard for measuring RV function - are difficult to analyze. Our aim was to investigate whether simple assessments of RV pressure-volume loop morphology and RV systolic pressure differential reflect PAH severity and RV function. We analyzed multi-beat RV pressure-volume loops (obtained by conductance catheterization with preload reduction) in 77 patients with PAH and 15 patients without pulmonary hypertension in two centers. Patients were categorized according to their pressure-volume loop shape (triangular, quadratic, trapezoid, or notched). RV systolic pressure differential was defined as end-systolic minus beginning-systolic pressure (ESP−BSP); augmentation index as ESP−BSP/pulse pressure; pulmonary arterial capacitance (PAC) as stroke volume/pulse pressure; and RV-arterial coupling as end-systolic/arterial elastance (Ees/Ea). Trapezoid and notched pressure-volume loops were associated with the highest afterload (Ea), augmentation index, pulmonary vascular resistance (PVR), mean pulmonary arterial pressure, stroke work, and B-type natriuretic peptide, and the lowest Ees/Ea and PAC. Multivariate linear regression identified Ea, PVR, and stroke work as the main determinants of ESP−BSP. ESP−BSP also significantly correlated with multi-beat Ees/Ea (Spearman's rho: −0.518, P < 0.001). A separate retrospective analysis of 113 patients with PAH showed that ESP−BSP obtained by routine right heart catheterization significantly correlated with a non-invasive surrogate of RV-arterial coupling (tricuspid annular plane systolic excursion/pulmonary arterial systolic pressure ratio; rho: −0.376, P < 0.001). In conclusion, pressure-volume loop shape and RV systolic pressure differential predominately depend on afterload and PAH severity and reflect RV-arterial coupling in PAH.

scholarly journals Enhanced NO-dependent pulmonary vasodilation limits increased vasoconstrictor sensitivity in neonatal chronic hypoxia

2017 ◽  
Vol 313 (4) ◽  
pp. H828-H838 ◽  
Author(s):  
Joshua R. Sheak ◽  
Laura Weise-Cross ◽  
Ray J. deKay ◽  
Benjimen R. Walker ◽  
Nikki L. Jernigan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Chronic Hypoxia ◽  
Systolic Pressure ◽  
Sprague Dawley ◽  
Ventricular Systolic Pressure ◽  
Pulmonary Vasodilation ◽  
Basal Tone

Augmented vasoconstrictor reactivity is thought to play an important role in the development of chronic hypoxia (CH)-induced neonatal pulmonary hypertension. However, whether this response to CH results from pulmonary endothelial dysfunction and reduced nitric oxide (NO)-mediated vasodilation is not well understood. We hypothesized that neonatal CH enhances basal tone and pulmonary vasoconstrictor sensitivity by limiting NO-dependent pulmonary vasodilation. To test this hypothesis, we assessed the effects of the NO synthase (NOS) inhibitor Nω-nitro-l-arginine (l-NNA) on baseline pulmonary vascular resistance (PVR) and vasoconstrictor sensitivity to the thromboxane mimetic U-46619 in saline -perfused lungs (in situ) from 2-wk-old control and CH (12-day exposure, 0.5 atm) Sprague-Dawley rats. Basal tone was defined as that reversed by exogenous NO (spermine NONOate). CH neonates displayed elevated right ventricular systolic pressure (in vivo) and right ventricular hypertrophy, indicative of pulmonary hypertension. Perfused lungs from CH rats demonstrated greater baseline PVR, basal tone, and U-46619-mediated vasoconstriction compared with control rats in the absence of l-NNA. l-NNA markedly increased baseline PVR and reactivity to U-46619 in lungs from CH neonates, further augmenting vasoconstrictor sensitivity compared with control lungs. Exposure to CH also enhanced NO-dependent vasodilation to arginine vasopressin, pulmonary expression of NOS III [endothelial NOS (eNOS)], and eNOS phosphorylation at activation residue Ser1177. However, CH did not alter lung nitrotyrosine levels, a posttranslational modification reflecting [Formula: see text] scavenging of NO. We conclude that, in contrast to our hypothesis, enhanced basal tone and agonist-induced vasoconstriction after neonatal CH is limited by increased NO-dependent pulmonary vasodilation resulting from greater eNOS expression and phosphorylation at activation residue Ser1177. NEW & NOTEWORTHY This research is the first to demonstrate enhanced nitric oxide-dependent vasodilation that limits increased vasoconstrictor reactivity in neonatal pulmonary hypertension. These results suggest that augmented vasoconstriction in this setting reflects changes in smooth muscle reactivity rather than a reduction in nitric oxide-dependent pulmonary vasodilation.

Sign in / Sign up

Export Citation Format

Share Document