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.

Neutral endopeptidase inhibition attenuates development of hypoxic pulmonary hypertension in rats

1993 ◽  
Vol 75 (4) ◽  
pp. 1615-1623 ◽  
Author(s):  
J. R. Klinger ◽  
R. D. Petit ◽  
R. R. Warburton ◽  
D. S. Wrenn ◽  
F. Arnal ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Pulmonary Arteries ◽  
Systolic Pressure ◽  
Weight Ratio ◽  
Neutral Endopeptidase ◽  
Mrna Levels ◽  
Hypoxic Pulmonary Hypertension ◽  
Ventricular Systolic Pressure ◽  
Nep Inhibition

Neutral endopeptidase (NEP) inhibition is thought to blunt hypoxic pulmonary hypertension by reducing atrial natriuretic peptide (ANP) metabolism, but this hypothesis has not been confirmed. We measured NEP activity, guanosine 3',5'-cyclic monophosphate (cGMP) production, plasma ANP levels, and cardiac ANP synthesis in rats given an orally active NEP inhibitor (SCH-34826) during 3 wk of hypoxia. Under normoxic conditions, SCH-34826 had no effect on plasma ANP levels but reduced pulmonary and renal NEP activity by 50% and increased urinary cGMP levels (60 +/- 6 vs. 22 +/- 4 pg/mg creatinine; P < 0.05). Under hypoxic conditions, SCH-34826-treated rats had lower plasma ANP levels (1,259 +/- 361 vs. 2,101 +/- 278 pg/ml; P < 0.05), lower right ventricular systolic pressure (53 +/- 5 vs. 73 +/- 2 mmHg; P < 0.05), lower right ventricle weight-to-left ventricle+septum weight ratio (0.47 +/- 0.04 vs. 0.53 +/- 0.03; P < 0.05), and less muscularization and percent medial wall thickness of peripheral pulmonary arteries (22 +/- 5 vs. 45 +/- 8% and 17 +/- 1 vs. 25 +/- 1%, respectively; P < 0.05 for all values) than did rats treated with vehicle alone. These values were not affected by SCH-34826 under normoxic conditions. SCH-34826 decreased right ventricular ANP tissue levels in hypoxic rats (27 +/- 10 vs. 8 +/- 1 ng/mg protein; P < 0.05) but did not affect steady-state ANP mRNA levels. We conclude that NEP inhibition blunts pulmonary hypertension without increasing plasma ANP levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Cystamine Treatment Fails to Prevent the Development of Pulmonary Hypertension in Chronic Hypoxic Rats

2021 ◽  
pp. 1-15
Author(s):  
Lars K. Markvardsen ◽  
Lene D. Sønderskov ◽  
Christine Wandall-Frostholm ◽  
Estéfano Pinilla ◽  
Judit Prat-Duran ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricle ◽  
Right Ventricular ◽  
Lung Tissue ◽  
Ventricular Hypertrophy ◽  
Systolic Pressure ◽  
Right Ventricular Hypertrophy ◽  
Ventricular Systolic Pressure ◽  
Pulmonary Arterial ◽  
The Right

<b><i>Introduction:</i></b> Pulmonary hypertension is characterized by vasoconstriction and remodeling of pulmonary arteries, leading to right ventricular hypertrophy and failure. We have previously found upregulation of transglutaminase 2 (TG2) in the right ventricle of chronic hypoxic rats. The hypothesis of the present study was that treatment with the transglutaminase inhibitor, cystamine, would inhibit the development of pulmonary arterial remodeling, pulmonary hypertension, and right ventricular hypertrophy. <b><i>Methods:</i></b> Effect of cystamine on transamidase activity was investigated in tissue homogenates. Wistar rats were exposed to chronic hypoxia and treated with vehicle, cystamine (40 mg/kg/day in mini-osmotic pumps), sildenafil (25 mg/kg/day), or the combination for 2 weeks. <b><i>Results:</i></b> Cystamine concentration-dependently inhibited TG2 transamidase activity in liver and lung homogenates. In contrast to cystamine, sildenafil reduced right ventricular systolic pressure and hypertrophy and decreased pulmonary vascular resistance and muscularization in chronic hypoxic rats. Fibrosis in the lung tissue decreased in chronic hypoxic rats treated with cystamine. TG2 expression was similar in the right ventricle and lung tissue of drug and vehicle-treated hypoxic rats. <b><i>Discussion/Conclusions:</i></b> Cystamine inhibited TG2 transamidase activity, but cystamine failed to prevent pulmonary hypertension, right ventricular hypertrophy, and pulmonary arterial muscularization in the chronic hypoxic rat.

scholarly journals The Glucagon-Like Peptide-1 Receptor Agonist Liraglutide Improves Hypoxia-Induced Pulmonary Hypertension in Mice Partly via Normalization of Reduced ETB Receptor Expression

2018 ◽  
pp. S175-S184 ◽  
Author(s):  
J. HONDA ◽  
T. KIMURA ◽  
S. SAKAI ◽  
H. MARUYAMA ◽  
K. TAJIRI ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Systolic Pressure ◽  
Receptor Expression ◽  
Vehicle Group ◽  
Ventricular Systolic Pressure ◽  
Etb Receptor ◽  
Mrna And Protein Expression ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
The Right

The glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide is an incretin hormone mimetic used in the treatment of diabetes. However, the effects of liraglutide on pulmonary hypertension (PH) and pulmonary endothelin (ET) system are unknown. Eight-week-old C57BL6/J mice were injected liraglutide or vehicle for 5 weeks. One week after injection, the mice were exposed to either room air (normoxia) or chronic hypoxia (10 % O2) for 4 weeks. The right ventricular systolic pressure (RVSP) was significantly higher in hypoxia + vehicle group than in normoxia + vehicle group. ET-1 mRNA expression in the lungs was comparable among all the groups. ETB mRNA and protein expression in the lungs was significantly lower in hypoxia + vehicle group than in normoxia + vehicle group. The above changes were normalized by liraglutide treatment. The expression of phospho-eNOS and phospho-AMPK proteins in the lungs was significantly higher in hypoxia + liraglutide group than in normoxia + vehicle group. We demonstrated for the first time that liraglutide effectively improved RVSP and RV hypertrophy in hypoxia-induced PH mice by activating eNOS through normalization of impaired ETB pathway and augmentation of AMPK pathway. Therefore, GLP-1R agonists can be promising therapeutic agents for PH.

Proposition of quantitative parameters for pre- and early post-operative assessment in pulmonary thromboendarterectomy – An Indian prospective study

2021 ◽  
pp. 021849232110421
Author(s):  
Krishnarao N Bhosle ◽  
Saptarshi Paul ◽  
Suraj W Nagre
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Systolic Pressure ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Pulmonary Artery Systolic Pressure ◽  
Walk Test ◽  
Pulmonary Thromboendarterectomy ◽  
Thromboembolic Pulmonary Hypertension

Introduction Chronic thromboembolic pulmonary hypertension results from the incomplete resolution of the vascular obstruction associated with pulmonary embolism. Symptoms are exertional dyspnoea and fatigue, and over a period of time, right ventricular dysfunction sets in. Pulmonary thromboendarterectomy is an effective surgical remedy for this condition. Our study is an initial post-operative experience of pulmonary thromboendarterectomy and we have also tried to formulate quantitative parameters for the prediction of the post-operative course in patients who are undergoing surgery. Methods Twenty patients with chronic thromboembolic pulmonary hypertension underwent pulmonary thromboendarterectomy between July 2017 and January 2020. Pre-operatively, each patient was subjected to the (i) 6-min walk test, (ii) pre-operative brain natriuretic peptide values and (iii) pulmonary artery systolic pressure. Following the surgery and subsequent discharge, the patients were followed up at intervals of 15 days, 1, 3, 6, 9 months and at 1 year. At one year post-operatively, the same three quantitative tests were performed on each subject. Results Post-operatively, the mean 6-min walk distance was 499.75 m as against 341.35 m pre-operatively ( p < 0.0001). Mean brain natriuretic peptide was 8.69 pm/l as against 47.58 pm/l pre-operatively ( p < 0.0001). Mean pulmonary artery systolic pressure was 22.25 as against 67.1 pre-operatively ( p < 0.0001). Conclusion 6-Min walk test, brain natriuretic peptide and pulmonary artery systolic pressure could be considered as useful predictors of the haemodynamic severity of disease and predict the post-operative outcome.

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.

Atrial natriuretic peptide expression in rats with different pulmonary hypertensive responses to hypoxia

1997 ◽  
Vol 273 (1) ◽  
pp. H411-H417 ◽  
Author(s):  
J. R. Klinger ◽  
D. S. Wrenn ◽  
R. R. Warburton ◽  
L. Pietras ◽  
L. C. Ou ◽  
...  
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Systolic Pressure ◽  
Weight Ratio ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Rat Strains ◽  
Ventricular Systolic Pressure ◽  
The Right ◽  
Atrial Natriuretic

Mechanisms that regulate atrial natriuretic peptide (ANP) expression during hypoxia are not well defined. We hypothesized that plasma immunoreactive ANP (irANP) and right heart irANP and ANP mRNA levels would be greater in a strain of Sprague-Dawley rats that develops more severe hypoxic pulmonary hypertension (H rats) than another strain (M rats). After 3 wk of hypoxia (0.5 atm), right ventricular systolic pressure (RVSP) and the right ventricle (RV) weight-to-left ventricle plus septum (LV (+) S) weight ratio [RV/(LV+S)] were greater in H rats than in M rats (70 +/- 4 vs. 40 +/- 2 mmHg and 0.59 +/- 0.02 vs. 0.50 +/- 0.02, respectively; P < 0.05 for both), but plasma ANP increased twofold and RV irANP and ANP mRNA increased fivefold in both rat strains. After 3 days of normoxic recovery from chronic hypoxia, RVSP, RV/(LV+S), and RV irANP and ANP mRNA levels decreased in M rats but not in H rats. Plasma irANP decreased to baseline levels in both rat strains. We conclude that, in addition to changes in RV pressure and hypertrophy, hypoxia acts through other mechanisms to modulate RV ANP synthesis and circulating ANP levels in hypoxia-adapted rats.

Brain natriuretic peptide: possible role in the modulation of hypoxic pulmonary hypertension

1994 ◽  
Vol 266 (3) ◽  
pp. L308-L315 ◽  
Author(s):  
N. S. Hill ◽  
J. R. Klinger ◽  
R. R. Warburton ◽  
L. Pietras ◽  
D. S. Wrenn
Keyword(s):  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Chronic Hypoxia ◽  
Mrna Levels ◽  
Vasorelaxant Effect ◽  
Pulmonary Vasodilator ◽  
Vasoconstrictor Response ◽  
Cardiac Gene ◽  
Isolated Lungs ◽  
The Right

To test the hypothesis that brain natriuretic peptide (BNP) plays a role similar to that of atrial natriuretic peptide (ANP) in modulating pulmonary vascular responses to hypoxia, we measured the vasodilator potency of ANP and BNP in rat pulmonary artery (PA) and thoracic aorta (TA) rings and in isolated rat lungs. We also measured the effect of chronic hypoxia on plasma levels and cardiac gene expression of both peptides. BNP had a vasorelaxant effect equipotent to that of ANP on preconstricted TA and PA rings, but was less potent than ANP in relaxing the vasoconstrictor response to hypoxia in isolated lungs [mean 50% inhibitory concentration (IC50) 10(-7) vs. 10(-6) M for ANP and BNP, respectively]. Plasma BNP levels were 30-fold lower than ANP, but both peptides increased approximately 70% during chronic hypoxia. In the right atrium, hypoxia lowered BNP mRNA slightly, but had no effect on ANP mRNA or tissue levels of either peptide. However, hypoxia increased right ventricular content and mRNA levels of both peptides by three- to fourfold. We conclude that BNP and ANP have similar pulmonary vasodilator effects and are upregulated proportionally during chronic hypoxia. These results support a role for BNP in modulating the pulmonary hypertensive response to chronic hypoxia.

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