Effects of continuous infusion of atrial natriuretic peptide on the pulmonary hypertension induced by chronic hypoxia in rats

1991 ◽  
Vol 81 (3) ◽  
pp. 379-385 ◽  
Author(s):  
L. Zhao ◽  
R. J. D. Winter ◽  
T. Krausz ◽  
J. M. B. Hughes
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Pulmonary Artery Pressure ◽  
Chronic Hypoxia ◽  
Systemic Blood Pressure ◽  
Artery Pressure ◽  
Pulmonary Vascular Remodelling ◽  
Atrial Natriuretic

1. The effects of the continuous infusion of atrial natriuretic peptide on the development of pulmonary hypertension were studied in rats exposed to chronic hypoxia. 2. Continuous intravenous infusion of two doses of synthetic rat atrial natriuretic peptide, 300 ng/h per rat (0.10 pmol/h per rat) and 800 ng/h per rat (0.28 pmol/h per rat), attenuated the development of pulmonary hypertension in rats exposed to chronic hypoxia (fractional concentration of oxygen in inspired air = 10%) for 7 days: (i) the pulmonary artery pressure (mean ± sd) in the vehicle-treated hypoxic group was 45 ± 6 mmHg compared with 28 ± 6 mmHg in the vehicle-treated normotoxic group (n = 8, P < 0.001); (ii) treatment with atrial natriuretic peptide in normoxia did not alter the pulmonary artery pressure, systemic blood pressure or heart rate; (iii) treatment with atrial natriuretic peptide in hypoxia resulted in a lower pulmonary artery pressure in the group treated with 800 ng of atrial natriuretic peptide/h per rat (38 ± 8 mmHg, P < 0.05 compared with the vehicle-treated hypoxic group) without affecting the systemic blood pressure or heart rate. 3. Chronic hypoxia resulted in an extension of vascular smooth muscle towards the periphery of the lung with the development of muscle in normally non-muscularized vessels (remodelling). Quantitative assessment of the small pulmonary vessels (external diameter 25–55 μm) showed that atrial natriuretic peptide treatment reduced pulmonary vascular remodelling in hypoxia (the percentage of thick-walled vessels in the peripheral lung hypoxic vehicle-treated group was 25 ± 6 compared with 19 ± 4 in the group given 300 ng of atrial natriuretic peptide/h per rat and 17 ± 7 in the group given 800 ng of atrial natriuretic peptide/h per rat, means ± sd, both P < 0.01 compared with the vehicle-treated normoxic group). 4. These data show that infusion of synthetic atrial natriuretic peptide attenuated the pulmonary vascular remodelling and associated pulmonary hypertension produced by chronic hypoxia.

Vasopressin Lowers Pulmonary Artery Pressure in Hypoxic Rats by Releasing Atrial Natriuretic Peptide

1989 ◽  
Vol 298 (4) ◽  
pp. 227-236 ◽  
Author(s):  
Hongkui Jin ◽  
Yiu-Fai Chen ◽  
Ren-Hui Yang ◽  
Robert M. Jackson ◽  
Suzanne Oparil ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Pulmonary Artery Pressure ◽  
Artery Pressure ◽  
Atrial Natriuretic

Atrial natriuretic peptide-induced relaxation of pre-constricted isolated rat perfused lungs: A comparison in control and hypoxia-adapted animals

1991 ◽  
Vol 81 (2) ◽  
pp. 201-208 ◽  
Author(s):  
A. G. Stewart ◽  
J. S. Thompson ◽  
T. K. Rogers ◽  
A. H. Morice
Keyword(s):  
Pulmonary Artery ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Pulmonary Artery Pressure ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Prostaglandin F2α ◽  
Artery Pressure ◽  
Pulmonary Vasoconstriction ◽  
Dose Dependent ◽  
Atrial Natriuretic

1. To further understand the vasodilator actions of atrial natriuretic peptide and its role in hypoxic pulmonary hypertension, we studied the effects of atrial natriuretic peptide in the isolated perfused rat lung during normoxic ventilation and after elevation of pulmonary artery pressure by either hypoxic ventilation or infusion of prostaglandin F2α. Control animals were compared with littermates that had become adapted to a 10% O2 environment for 3 weeks. Atrial natriuretic peptide was compared with atriopeptin I and atriopeptin III in order to study its structure-activity relationship. 2. Five experiments, each involving six control and six chronically hypoxic rats, were performed. During normoxic ventilation, atrial natriuretic peptide (30 ng-3 μg) produced a dose-dependent reduction in pulmonary artery pressure in chronically hypoxic rats, but had no action in the control animals. 3. Atrial natriuretic peptide dose-dependently abolished hypoxic pulmonary vasoconstriction to a greater extent in chronically hypoxic rats (EC50 98 ng) than in control rats (EC50 298 ng; P < 0.001). Bolus atrial natriuretic peptide (100 ng) produced a plasma concentration of 22.6 pmol/l at 1 min, which is within the pathophysiological range. Initial plasma atrial natriuretic peptide levels were 9.4 pmol/l in control animals and 27.4 pmol/l in chronically hypoxic rats. 4. Chronically hypoxic rats were more sensitive to atriopeptin I, atriopeptin III and atrial natriuretic peptide than were the control rats (P < 0.05). Atrial natriuretic peptide and atriopeptin III were equipotent and were 10 times more potent than atriopeptide I in both groups (P < 0.001). 5. Although atrial natriuretic peptide lowered pulmonary artery pressure in isolated perfused lungs pre-constricted with prostaglandin F2α (5 μg/min), there was no difference between the control and chronically hypoxic groups, and the EC50 296 ng in the chronically hypoxic rats was significantly (P < 0.001) less than that seen in the chronically hypoxic despite similar levels of induced constriction by the two stimuli. 6. A set dose of atrial natriuretic peptide produced the same percentage reduction in hypoxic pulmonary vasoconstriction despite differing levels of pre-constriction produced by ventilating with 7%, 5%, 3% or 0% O2. There was no change in the arterial partial pressure of O2 or the alveolar-arterial gradient after injection of atrial natriuretic peptide, suggesting that its effects are not due to a reduction in pulmonary oedema. 7. Atrial natriuretic peptide relaxes pre-constricted pulmonary arteries in the isolated perfused rat lung in a dose-dependent manner within the pathophysiological range. The greater action of atrial natriuretic peptide in chronic hypoxia could be due to its action at the new sites of hypoxic pulmonary vasoconstriction, the newly muscularized alveolar arteries which develop during adaptation to hypoxia.

Cardioprotective and vasomotor effects of HO activity during acute and chronic hypoxia

2004 ◽  
Vol 287 (5) ◽  
pp. H2009-H2015 ◽  
Author(s):  
Cynthia L. Hartsfield ◽  
Ivan F. McMurtry ◽  
D. Dunbar Ivy ◽  
Kenneth G. Morris ◽  
Shanda Vidmar ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Pulmonary Artery Pressure ◽  
Carotid Arteries ◽  
Chronic Hypoxia ◽  
Acute Hypoxia ◽  
Left Ventricular ◽  
Artery Pressure ◽  
Tin Protoporphyrin ◽  
Rv Function

Prolonged hypoxia leads to the development of pulmonary hypertension. Recent reports have suggested enhancement of heme oxygenase (HO), the major source of intracellular carbon monoxide (CO), prevents hypoxia-induced pulmonary hypertension and vascular remodeling in rats. Therefore, we hypothesized that inhibition of HO activity by tin protoporphyrin (SnPP) would exacerbate the development of pulmonary hypertension. Rats were injected weekly with either saline or SnPP (50 μmol/kg) and exposed to hypobaric hypoxia or room air for 5 wk. Pulmonary and carotid arteries were catheterized, and animals were allowed to recover for 48 h. Pulmonary and systemic pressures, along with cardiac output, were recorded during room air and acute 10% O2 breathing in conscious rats. No difference was detected in pulmonary artery pressure between saline- and SnPP-treated animals in either normoxic or hypoxic groups. However, blockade of HO activity altered both systemic and pulmonary vasoreactivity to acute hypoxic challenge. Despite no change in baseline pulmonary artery pressure, all rats treated with SnPP had decreased ratio of right ventricular (RV) weight to left ventricular (LV) plus septal (S) weight (RV/LV + S) compared with saline-treated animals. Echocardiograms suggested dilatation of the RV and decreased RV function in hypoxic SnPP-treated rats. Together these data suggest that inhibition of HO activity and CO production does not exacerbate pulmonary hypertension, but rather that HO and CO may be involved in mediating pulmonary and systemic vasoreactivity to acute hypoxia and hypoxia-induced RV function.

Effects of the Neutral Endopeptidase Inhibitor, SCH 42495, on the Cardiovascular Remodelling Secondary to Chronic Hypoxia in Rats

1994 ◽  
Vol 87 (1) ◽  
pp. 109-114 ◽  
Author(s):  
J. S. Thompson ◽  
W. Sheedy ◽  
A. H. Morice
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Chronic Hypoxia ◽  
Neutral Endopeptidase ◽  
Pulmonary Vasculature ◽  
Vascular Remodelling ◽  
Plasma Atrial Natriuretic Peptide ◽  
And Control ◽  
Pulmonary Vascular Remodelling ◽  
Atrial Natriuretic

1. We have investigated the effects of inhibition of neutral endopeptidase on the cardiovascular remodelling secondary to chronic hypoxia in rats using a novel neutral endopeptidase inhibitor, SCH 42495. 2. Rats were divided into four groups, two of which were maintained in a normobaric, hypoxic chamber (10% O2) and two in room air. Animals received either neutral endopeptidase inhibitor, SCH 42495 (30 mg/kg), or aqueous methyl cellulose vehicle (0.4%) twice daily by oral gavage. 3. At 1, 3, 7, 10 and 14 days, animals (n = 4 per group for days 1, 3, 7 and 14, and n =8 for day 10) were killed. Hearts were dissected and weighed for determination of ventricular ratios, lungs were perfused with formol saline for histological examination of the pulmonary vasculature, and blood was collected for measurement of plasma atrial natriuretic peptide level. 4. Treatment with SCH 42495 caused a significant reduction in the pulmonary vascular remodelling and ventricular hypertrophy in hypoxic rats after 10 days. Plasma atrial natriuretic peptide levels were significantly elevated in both SCH 42495-treated and control hypoxic animals (n = 8) after 10 days when compared with the normoxic groups. However, there was no difference in plasma ANP levels between SCH 42495-treated and control chronic hypoxic groups at day 10. 5. Treatment with SCH 42495 leads to a decrease in cardiovascular remodelling secondary to chronic hypoxia in rats. A local action of atrial natriuretic peptide within the pulmonary vasculature may be responsible for this effect. Modulation of atrial natriuretic peptide may have therapeutic potential in the management of conditions characterized by pulmonary hypertension and pulmonary vascular remodelling.

scholarly journals Hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELMα) induces the vascular and hemodynamic changes of pulmonary hypertension

2009 ◽  
Vol 296 (4) ◽  
pp. L582-L593 ◽  
Author(s):  
Daniel J. Angelini ◽  
Qingning Su ◽  
Kazuyo Yamaji-Kegan ◽  
Chunling Fan ◽  
John T. Skinner ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Pulmonary Vascular Resistance ◽  
Pulmonary Artery Pressure ◽  
Vascular Resistance ◽  
Vascular Remodeling ◽  
Chronic Hypoxia ◽  
Heart Hypertrophy ◽  
Right Heart ◽  
Artery Pressure

Pulmonary hypertension (PH) is a serious disease of multiple etiologies mediated by hypoxia, immune stimuli, and elevated pulmonary pressure that leads to vascular thickening and eventual right heart failure. In a chronic hypoxia model of PH, we previously reported the induction of a novel pleiotropic cytokine, hypoxia-induced mitogenic factor (HIMF), that exhibits mitogenic, vasculogenic, contractile, and chemokine properties during PH-associated vascular remodeling. To examine the role of HIMF in hypoxia-induced vascular remodeling, we performed in vivo knockdown of HIMF using short hairpin RNA directed at rat HIMF in the chronic hypoxia model of PH. Knockdown of HIMF partially blocked increases in mean pulmonary artery pressure, pulmonary vascular resistance, right heart hypertrophy, and vascular remodeling caused by chronic hypoxia. To demonstrate a direct role for HIMF in the mechanism of PH development, we performed HIMF-gene transfer into the lungs of rats using a HIMF-expressing adeno-associated virus (AAV). AAV-HIMF alone caused development of PH similar to that of chronic hypoxia with increased mean pulmonary artery pressure and pulmonary vascular resistance, right heart hypertrophy, and neomuscularization and thickening of small pulmonary arterioles. The findings suggest that HIMF represents a critical cytokine-like growth factor in the development of PH.

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